HIV InfectionsPhase 1NCT00991224
Redirected High Affinity Gag-Specific Autologous T Cells for HIV Gene Therapy
A Phase 1 study testing WT-gag-TCR modified T cells, α/6-gag-TCR modified T cells and STI or Drug Holiday in people with HIV Infections, 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. T-cells are one of the white blood cells used by the body to fight HIV. CD8 T-cells are a type of T-cell used by the body to detect and kill cells which have been infected by foreign viruses or organisms, including the HIV virus. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- WT-gag-TCR modified T cells, α/6-gag-TCR modified T cells and STI or Drug Holiday
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to Jan 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
- Age 18 years or older
- Karnofsky Performance of 80 or higher
- HLA-A2 Positive
- Chronic HIV-1 infection
- On stable HAART regimen (with no changes within 4 weeks of study entry)
- Willing to undergo a limited treatment interruption of antiretroviral medication
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- CD4+ T cell count ≥450 cells/mm3
- Documented CD4 nadir of ≥200 cells/mm3
- Undetectable HIV-1 RNA
- ARMS 1 and 2 only, at least a singe documented historic viral load set point reading
- Lab Values: Hgb≥10 males; ≥9.5 females ; ANC≥1000/mm3 ; Platelets≥1000,000/mm3 ; Creatinine≤1.5 mg/dL ; AST, ALT ≤ 2.5xULN
Who cannot join
- Current or prior AIDS diagnosis
- Previous participation in any gene therapy using an integrating vector (subjects treated with Placebo will not be excluded)
- History of cancer or malignancy (allowed to have successfully treated basal cell or squamous cell carcinoma of the skin)
- Have history or current exam indicative of active or unstable cardiac disease or hemodynamic instability
- Have history or current exam indicative of bleeding diathesis
- Previous treatment with any HIV experimental vaccine within 6 months prior to screening
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- Use of chronic corticosteroids, hydroxyurea or immunomodulating agents such as IL2, interferon alpha, interferon gamma, granulocyte colony stimulating factors within 30 days prior to study entry (inhaled steroids are not exclusionary)
- Currently breast feeding, pregnant or unwilling to use acceptable methods of birth control
- 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/dependence
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry
- Receipt of a vaccination within 30 days prior to study entry
- Have a known allergy or hypersensitivity to human serum albumin, DMSO or Dextran 40
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, Open Label, Multi Arm, Single Ctr Study to Evaluate Safety & Tolerability of Escalating Doses of Autologous T Cells Modified With Lentiviral Vectors Expressing High Affinity Gag-specific TCRS in HLA-A02 Patients With HIV
This research study is being carried out to study a new way to possibly treat HIV. T-cells are one of the white blood cells used by the body to fight HIV. CD8 T-cells are a type of T-cell used by the body to detect and kill cells which have been infected by foreign viruses or organisms, including the HIV virus. CD8 T-cells must identify the HIV virus in order to kill it. Because HIV is constantly changing the way it looks to the CD8 T-cells, some of the HIV virus escapes detection and is not killed by the CD8 T-cells.
This research study uses a T cell receptor (TCR) protein specific for HIV (SL9 TCR) and adds it to the CD8 T-cells in the laboratory in order to help the CD8 T-cells recognize the constantly changing HIV virus and make it able to fight HIV more efficiently. TCR stands for T cell receptor. TCRs are found on the surface of T cells and allow the T cells to recognize other cells. Laboratory studies have shown that when CD8 T-cells are modified with SL9 TCRs, they kill cells that are infected with HIV better than normal CD8 T-cells can. On the basis of these laboratory results, there is the potential that SL9 TCRs may work in people infected with HIV and improve their immune system by killing HIV infected cells and thus may help control HIV infection.
Read more
Two different SL9 TCRs will be tested in this study, WT-gag-TCR and α/6-gag-TCR. Two different types of SL9 TCRs are being used in this research study because the laboratory studies suggest that the different SL9 TCRs will function differently depending on the amount of virus in your body. A goal of this clinical study is to test the effects of infusions of either SL9 TCR in the presence or absence of a viral load.
All subjects who receive WT-gag-TCR or the α/6-gag-TCR T cells will be enrolled in a Long Term Follow up study to monitor subjects. Subjects will be followed every 6 months for five years following the 1st infusion of the T cells. If the WT-gag-TCR or the α/6-gag-TCR T cells are no longer found in the blood after five years, then subjects will be contacted yearly for the next 10 years. If the WT-gag-TCR or the α/6-gag-TCR T cells are found in the blood at five years after the 1st infusion of T cells, then the subjects will continue to be seen once a year until the WT-gag-TCR or the α/6-gag-TCR T cells are no longer found in the blood for a maximum of 15 years.
Read the detailed description
See Above
- Conditions
- HIV Infections
- Being tested
- WT-gag-TCR modified T cells, α/6-gag-TCR modified T cells, STI or Drug Holiday
- Keywords
- HIV, HIV therapeutic vaccine
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WT-gag-TCR modified T cellsBiological
Single dose of WT-gag-TCR modified T cells infused over 3 consecutive days.
α/6-gag-TCR modified T cellsBiological
Single dose of WT-gag-TCR modified T cells infused over 3 consecutive days.
STI or Drug HolidayOther
Subjects will stop taking antiviral medications for 16 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Subjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 at the time of enrollment, a CD4 nadir >200 and a recorded historical viral load setpoint, will receive a WT-gag-TCR modified autologous T cells, followed one week later by a 16 week treatment interruption. Receives: Biological: WT-gag-TCR modified T cells; Other: STI or Drug Holiday |
| Arm 2 | Experimental | Subjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 at the time of enrollment, a CD4 nadir >200 and a recorded historical viral load setpoint, will receive a α/6-gag-TCR modified autologous T cells, followed one week later by a 16 week treatment interruption. Receives: Biological: α/6-gag-TCR modified T cells; Other: STI or Drug Holiday |
| Arm 3 | Experimental | Subjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 and a CD4 nadir >200. Subject will undergo an 16 week treatment interruption during which a single infusion of WT-gag-TCR modified autologous T cells at 8 weeks post STI. Receives: Biological: WT-gag-TCR modified T cells; Other: STI or Drug Holiday |
| Arm 4 | Experimental | Subjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 and a CD4 nadir of >200. Subject will undergo a 16-week treatment interruption during which a single infusion of α/6-gag-TCR modified autologous T cells at 8 weeks post STI. Receives: Biological: α/6-gag-TCR modified T cells; Other: STI or Drug Holiday |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine optimal dose and to evaluate the safety and tolerability of the study drug.
Measured: 3 years from end of study
To monitor for delayed adverse events associated with lentiviral vector gene transfer (RCL and insertional oncogenesis)
Measured: 3 years from end of study
Secondary outcomes (2)
To determine the antiviral effects of WT-gag-and α/6-gag- TCR transduced cells in patients with low and high antigen load (presence and absence of viremia)
Measured: 3 years from end of study
To monitor engraftment of vector modified cells in the peripheral circulation
Measured: 3 years from end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2009 (estimated)
- Study startNov 2009
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Adaptimmune
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00991224
- Sponsor's protocol ID
- 810108
- Status last verified
- Dec 2017
- First submitted
- 6 Oct 2009
- Last updated
- 10 Oct 2019
- 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 10 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot, Open Label, Multi Arm, Single Ctr Study to Evaluate Safety & Tolerability of Escalating Doses of Autologous T Cells Modified With Lentiviral Vectors Expressing High Affinity Gag-specific TCRS in HLA-A02 Patients With HIV
- ClinicalTrials.gov ID
- NCT00991224
- Acronym / sponsor ID
- 810108
- Conditions
- HIV Infections
- Keywords
- HIV, HIV therapeutic vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Adaptimmune
- Study start
- Nov 2009
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 7 Oct 2009 (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. T-cells are one of the white blood cells used by the body to fight HIV. CD8 T-cells are a type of T-cell used by the body to detect and kill cells which have been infected by foreign viruses or organisms, including the HIV virus. CD8 T-cells must identify the HIV virus in order to kill it. Because HIV is constantly changing the way it looks to the CD8 T-cells, some of the HIV virus escapes detection and is not killed by the CD8 T-cells.
This research study uses a T cell receptor (TCR) protein specific for HIV (SL9 TCR) and adds it to the CD8 T-cells in the laboratory in order to help the CD8 T-cells recognize the constantly changing HIV virus and make it able to fight HIV more efficiently. TCR stands for T cell receptor. TCRs are found on the surface of T cells and allow the T cells to recognize other cells. Laboratory studies have shown that when CD8 T-cells are modified with SL9 TCRs, they kill cells that are infected with HIV better than normal CD8 T-cells can. On the basis of these laboratory results, there is the potential that SL9 TCRs may work in people infected with HIV and improve their immune system by killing HIV infected cells and thus may help control HIV infection.
Two different SL9 TCRs will be tested in this study, WT-gag-TCR and α/6-gag-TCR. Two different types of SL9 TCRs are being used in this research study because the laboratory studies suggest that the different SL9 TCRs will function differently depending on the amount of virus in your body. A goal of this clinical study is to test the effects of infusions of either SL9 TCR in the presence or absence of a viral load.
All subjects who receive WT-gag-TCR or the α/6-gag-TCR T cells will be enrolled in a Long Term Follow up study to monitor subjects. Subjects will be followed every 6 months for five years following the 1st infusion of the T cells. If the WT-gag-TCR or the α/6-gag-TCR T cells are no longer found in the blood after five years, then subjects will be contacted yearly for the next 10 years. If the WT-gag-TCR or the α/6-gag-TCR T cells are found in the blood at five years after the 1st infusion of T cells, then the subjects will continue to be seen once a year until the WT-gag-TCR or the α/6-gag-TCR T cells are no longer found in the blood for a maximum of 15 years.
Detailed description
See Above
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Biological: WT-gag-TCR modified T cells, Other: STI or Drug HolidaySubjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 at the time of enrollment, a CD4 nadir >200 and a recorded historical viral load setpoint, will receive a WT-gag-TCR modified autologous T cells, followed one week later by a 16 week treatment interruption. |
| Arm 2 | Experimental | Biological: α/6-gag-TCR modified T cells, Other: STI or Drug HolidaySubjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 at the time of enrollment, a CD4 nadir >200 and a recorded historical viral load setpoint, will receive a α/6-gag-TCR modified autologous T cells, followed one week later by a 16 week treatment interruption. |
| Arm 3 | Experimental | Biological: WT-gag-TCR modified T cells, Other: STI or Drug HolidaySubjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 and a CD4 nadir >200. Subject will undergo an 16 week treatment interruption during which a single infusion of WT-gag-TCR modified autologous T cells at 8 weeks post STI. |
| Arm 4 | Experimental | Biological: α/6-gag-TCR modified T cells, Other: STI or Drug HolidaySubjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 and a CD4 nadir of >200. Subject will undergo a 16-week treatment interruption during which a single infusion of α/6-gag-TCR modified autologous T cells at 8 weeks post STI. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18 years or older
- Karnofsky Performance of 80 or higher
- HLA-A2 Positive
- Chronic HIV-1 infection
- On stable HAART regimen (with no changes within 4 weeks of study entry)
Key exclusion criteria (13 listed)
- Current or prior AIDS diagnosis
- Previous participation in any gene therapy using an integrating vector (subjects treated with Placebo will not be excluded)
- History of cancer or malignancy (allowed to have successfully treated basal cell or squamous cell carcinoma of the skin)
- Have history or current exam indicative of active or unstable cardiac disease or hemodynamic instability
- Have history or current exam 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 |
|---|---|---|
| WT-gag-TCR modified T cellsSingle dose of WT-gag-TCR modified T cells infused over 3 consecutive days. | Biological | Arm 1, Arm 3 |
| α/6-gag-TCR modified T cellsSingle dose of WT-gag-TCR modified T cells infused over 3 consecutive days. | Biological | Arm 2, Arm 4 |
| STI or Drug HolidaySubjects will stop taking antiviral medications for 16 weeks. | Other | Arm 1, Arm 2, Arm 3, Arm 4 |
Primary outcome
To determine optimal dose and to evaluate the safety and tolerability of the study drug.
Time frame: 3 years from end of study
To monitor for delayed adverse events associated with lentiviral vector gene transfer (RCL and insertional oncogenesis)
Time frame: 3 years from end of study
2 secondary outcomes
To determine the antiviral effects of WT-gag-and α/6-gag- TCR transduced cells in patients with low and high antigen load (presence and absence of viremia)
Time frame: 3 years from end of study
To monitor engraftment of vector modified cells in the peripheral circulation
Time frame: 3 years from end of study
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 10 Oct 2019.
- UPenn AIDS Clinical Trials Unit (ACTU) WebsiteLink provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 WT-gag-TCR modified T cells, α/6-gag-TCR modified T cells and STI or Drug Holiday in people with HIV Infections, 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 11 inclusion and 13 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 10 Oct 2019. 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?
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?
To determine optimal dose and to evaluate the safety and tolerability of the study drug. (time frame: 3 years from end of study). The study lists 2 primary outcomes in all. 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 10 Oct 2019.