HivEarly Phase 1NCT03020524
Autologous CD4 T-Cells in HIV (C34-CXCR4)
A Early Phase 1 study testing Autologous CD4 T-Cells in people with Hiv, run by University of Pennsylvania at 1 site in United States.
Trial summary
A single cohort, open-label pilot study of the safety and tolerability of a single infusion of autologous CD4+ T-cells genetically modified with an HR2, C34-peptide conjugated to the CXCR4 N-terminus using a lentiviral vector in HIV-infected subjects. This is a first in human study of C34-CXCR4 T 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?
- Autologous CD4 T-Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to Mar 2020
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to enrollment and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL.
- Ability and willingness of subject to provide informed consent.
- Men and women ages ≥18 years.
- Clinically stable on their first or second HAART regimen. Changes while the patient HIV viral load is undetectable does not count toward the number of ART regimens used, only changes made for virologic failure (for example an individual switching from an NNRTI-based regimen to an integrase inhibitor based regimen while the HIV viral load is undetectable will still be in their first regimen). Site investigator anticipates that a fully active alternative ART regimen could be constructed in the event of virologic failure on the current ART regimen.The current regimen should have no changes within 4 weeks of enrollment. Subjects must be willing to continue on current antiretroviral therapy for the duration of the study except for the duration of the 16 week analytical treatment interruption. (NOTE: changes to safely begin the treatment interruption are permitted).
- Screening HIV-1 RNA that is ≤50 copies/mL using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent within 30 days prior to enrollment.
- HIV-1 RNA ≤50 copies/mL using a FDA-approved assay for at least 24 weeks prior to enrollment performed by any laboratory that has a CLIA certification or its equivalent.
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- NOTE: HIV-RNA must be measured at least once in the last 24 weeks and at least 3 days before the screening measure. Single determinations that are between >50 and <400 copies/mL (ie, blips) are allowed as long as the preceding and subsequent determinations are ≤50 copies/mL. The screening value may serve as the subsequent determination ≤50 copies/mL following a blip
- NOTE: subjects who have participated in other trials using ATI's will be permitted since detectable virus during the interruption does not represent virologic failure. These subjects should have at least 24 weeks of VL <50 copies/mL.
- Screening CD4+ T-cell count ≥450 cells/ mm3 within 30 days of enrollment.
- Started ART with nadir CD4+ ≥200 cells/ mm3.
- The following laboratory values obtained within 30 days prior to enrollment meeting the following criteria:
- Absolute neutrophil count (ANC) ≥1000 cells/mm3
- Hemoglobin:≥10.0(males); ≥9.5 (females) g/dL
- Platelet count: 100,000/mm3
- Calculated creatinine clearance ≥50 mL/min estimated by the Cockcroft-Gault equation
- Alanine aminotransferase (ALT) ≤ 2.0 x ULN
- Negative HBsAg within 6 months prior to enrollment.
- Negative HCV serology, or if positive, negative HCV RNA within 6 months prior to enrollment
- Adequate venous access and no other contraindications for leukapheresis.
- Have a Karnofsky Performance Score of 70 or higher.
- 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.
- NOTE: Subjects with a history of cardiac disease may participate with a physician's approval.
- History or any features on physical examination indicative of a bleeding diathesis
Show all 18Show fewer
- Have been previously treated with any HIV experimental vaccine within 6 months prior to enrollment, or any previous gene therapy using an integrating vector.
- NOTE: Subjects treated with placebo in an HIV vaccine study will not be excluded if documentation that they received placebo is provided.
- Use of chronic systemic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to enrollment.
- NOTE: Recent or current use of inhaled steroids is not exclusionary. If subjects are prescribed a brief course of oral corticosteroids, the use should be limited to less than 7 days. Use of steroids before apheresis and immune assessment blood draws should be discouraged as it will affect white blood cell function.
- 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 site investigator, would interfere with adherence to study requirements.
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to enrollment
- Asymptomatic baseline serum chemistry elevations in LFTs, bilirubin, and serum creatinine due to HAART medication are not exclusionary, when in the opinion of the investigator, the abnormalities are not attributable to intrinsic hepatorenal disease. Such baseline elevations must be due to HAART.
- Receipt of vaccination within 30 days prior to enrollment.
- NOTE: It is recommended that subjects enrolling into this study should have completed their routine vaccinations (hepatitis A, hepatitis B, pneumococcus, and tetanus diphtheria booster) at least 30 days prior to enrollment
- Have an allergy or hypersensitivity to study product excipients (human serum albumin, DMSO and 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 Study to Evaluate the Safety and Tolerability of Escalating Doses of Autologous CD4 T-Cells Modified With Lentiviral Vector Expressing an HR2, C34-peptide Conjugated to the CXCR4 N-terminus in HIV-infected Subjects
A single cohort, open-label pilot study of the safety and tolerability of a single infusion of autologous CD4+ T-cells genetically modified with an HR2, C34-peptide conjugated to the CXCR4 N-terminus using a lentiviral vector in HIV-infected subjects. This is a first in human study of C34-CXCR4 T cells
Read the detailed description
There will be a single cohort in this study, which consists of subjects with well-controlled HIV replication on HAART. Within this cohort will be 3 escalating doses of T-cell infusions. A modified 3+3+3 dose-escalation design will be followed, in which the standard dose-escalation algorithm is stopped when a maximum of 9 evaluable subjects or a DLT stopping point has been reached, whichever comes first. At each dose level, three patients are treated. For dose levels 1 and 2, if 0/3 subjects have a dose limiting toxicity (DLT), then the dose is escalated. If 1/3 has a DLT (grade 3 or higher unexpected, related adverse event [AE]) at a dose level then 3 additional patients are treated at that dosage before escalating, and if <2/6 have DLT (i.e. no additional DLT is observed) then the dose is escalated to the next planned dose level and patients treated until a maximum of 9 evaluable subjects has been reached. The study will comprise of 5 steps:
Step 1, all participants will undergo leukapheresis to obtain CD4 positive T-cells that will be genetically modified. A second leukapheresis and a rectal biopsy will provide baseline specimens to evaluate the size of the HIV reservoir
Step 2, all participants will receive a single infusion of C34-CXCR4-modified CD4+ T-cells at one of 3 dose levels. The first 3 subjects will receive dose level 1 of 0.8-1x109 transduced CD4+T-cells. Provided no dose limiting toxicity (DLT) is seen at the first dose level, the next 3 subjects will receive infusion at the 2nd dose level of 2.4-3x109 transduced CD4+ T-cells. If no DLT occurs at that dose, the final 3 subjects will receive the 3rd dose level of 0.8-1x1010 transduced CD4+ T-cells. In the event of a DLT (grade 3 or higher unexpected, related AE) recruitment will be paused pending DSMB decision.
Step 3 all participants will participate in a 16-week analytical treatment interruption beginning 4 weeks after T-cell infusion.
At the end of step 3 all participants will undergo mini-leukapheresis and rectal biopsy
Step 4 all participants will be advised to resume antiretroviral therapy and will be followed until plasma HIV RNA falls below the limit of detection.
In Step 5 all participants will undergo leukapheresis and rectal biopsy at 52 weeks post infusion. At the completion of the study, participants will be asked to participate in a long-term follow-up study as required by regulatory authorities.
- Conditions
- Hiv
- Being tested
- Autologous CD4 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.
Autologous CD4 T-CellsBiological
all participants will receive a single infusion of C34-CXCR4-modified CD4+ T-cells at one of 3 dose levels. The first 3 subjects will receive dose level 1 of 0.8-1x109 transduced CD4+T-cells. Provided no dose limiting toxicity (DLT) is seen at the first dose level, the next 3 subjects will receive infusion at the 2nd dose level of 2.4-3x109 transduced CD4+ T-cells. If no DLT occurs at that dose, the final 3 subjects will receive the 3rd dose level of 0.8-1x1010 transduced CD4+ T-cells. In the event of a DLT (grade 3 or higher unexpected, related AE) recruitment will be paused pending DSMB decision
| Study group | Role | What they receive |
|---|---|---|
| Dose level 1: | Experimental | Autologous CD4 T-Cells0.8-1x10^9 transduced CD4+T-cells administered IV as a single dose Receives: Biological: Autologous CD4 T-Cells |
| Dose level 2 | Active comparator | Autologous CD4 T-Cells 2.4-3x10^9 transduced CD4+ T-cells administered IV as a single dose Receives: Biological: Autologous CD4 T-Cells |
| Dose level 3 | Active comparator | Autologous CD4 T-Cells 0.8-1x10^10 transduced CD4+ T-cells administered IV as a single dose Receives: Biological: Autologous CD4 T-Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Subjects With Treatment Related Adverse Events
assessed by DAIDS AE grading table v2.0 November 2014
Measured: one year
Secondary outcomes (4)
Compare the Percentage of Enriched Modified Cells C34-CXCR4 Modifiec T- Cells
Measured: 2 weeks post infusion, prior to ARV reinitiation, weeks 12, 16 and 20
Compare the Change Between CD4 Count
Measured: Baseline, week 2 post infusion, prior to ARV initiation, weeks 12, 16 20
Compare Viral Set Point Log 10 HIV RNA Level
Measured: week 2 post infusion, prior to ARV initiation, week 12, 16, 20
Evaluate Cell Mediated Response (Immunogenicity) Using Flow Cytometry
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 posted13 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionNov 2019
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 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 Pennaylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03020524
- Sponsor's protocol ID
- 826035
- Status last verified
- Nov 2022
- First submitted
- 9 Jan 2017
- Last updated
- 15 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Evaluate the Safety and Tolerability of Escalating Doses of Autologous CD4 T-Cells Modified With Lentiviral Vector Expressing an HR2, C34-peptide Conjugated to the CXCR4 N-terminus in HIV-infected Subjects
- ClinicalTrials.gov ID
- NCT03020524
- Acronym / sponsor ID
- 826035
- Conditions
- Hiv
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- Nov 2019 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 13 Jan 2017 (estimated)
- Results
- Posted 9 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A single cohort, open-label pilot study of the safety and tolerability of a single infusion of autologous CD4+ T-cells genetically modified with an HR2, C34-peptide conjugated to the CXCR4 N-terminus using a lentiviral vector in HIV-infected subjects. This is a first in human study of C34-CXCR4 T cells
Detailed description
There will be a single cohort in this study, which consists of subjects with well-controlled HIV replication on HAART. Within this cohort will be 3 escalating doses of T-cell infusions. A modified 3+3+3 dose-escalation design will be followed, in which the standard dose-escalation algorithm is stopped when a maximum of 9 evaluable subjects or a DLT stopping point has been reached, whichever comes first. At each dose level, three patients are treated. For dose levels 1 and 2, if 0/3 subjects have a dose limiting toxicity (DLT), then the dose is escalated. If 1/3 has a DLT (grade 3 or higher unexpected, related adverse event [AE]) at a dose level then 3 additional patients are treated at that dosage before escalating, and if <2/6 have DLT (i.e. no additional DLT is observed) then the dose is escalated to the next planned dose level and patients treated until a maximum of 9 evaluable subjects has been reached. The study will comprise of 5 steps:
Step 1, all participants will undergo leukapheresis to obtain CD4 positive T-cells that will be genetically modified. A second leukapheresis and a rectal biopsy will provide baseline specimens to evaluate the size of the HIV reservoir
Step 2, all participants will receive a single infusion of C34-CXCR4-modified CD4+ T-cells at one of 3 dose levels. The first 3 subjects will receive dose level 1 of 0.8-1x109 transduced CD4+T-cells. Provided no dose limiting toxicity (DLT) is seen at the first dose level, the next 3 subjects will receive infusion at the 2nd dose level of 2.4-3x109 transduced CD4+ T-cells. If no DLT occurs at that dose, the final 3 subjects will receive the 3rd dose level of 0.8-1x1010 transduced CD4+ T-cells. In the event of a DLT (grade 3 or higher unexpected, related AE) recruitment will be paused pending DSMB decision.
Step 3 all participants will participate in a 16-week analytical treatment interruption beginning 4 weeks after T-cell infusion.
At the end of step 3 all participants will undergo mini-leukapheresis and rectal biopsy
Step 4 all participants will be advised to resume antiretroviral therapy and will be followed until plasma HIV RNA falls below the limit of detection.
In Step 5 all participants will undergo leukapheresis and rectal biopsy at 52 weeks post infusion. At the completion of the study, participants will be asked to participate in a long-term follow-up study as required by regulatory authorities.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose level 1: | Experimental | Biological: Autologous CD4 T-CellsAutologous CD4 T-Cells0.8-1x10^9 transduced CD4+T-cells administered IV as a single dose |
| Dose level 2 | Active comparator | Biological: Autologous CD4 T-CellsAutologous CD4 T-Cells 2.4-3x10^9 transduced CD4+ T-cells administered IV as a single dose |
| Dose level 3 | Active comparator | Biological: Autologous CD4 T-CellsAutologous CD4 T-Cells 0.8-1x10^10 transduced CD4+ T-cells administered IV as a single dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to enrollment and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL.
- Ability and willingness of subject to provide informed consent.
- Men and women ages ≥18 years.
- Clinically stable on their first or second HAART regimen. Changes while the patient HIV viral load is undetectable does not count toward the number of ART regimens used, only changes made for virologic failure (for example an individual switching from an NNRTI-based regimen to an integrase inhibitor based regimen while the HIV viral load is undetectable will still be in their first regimen). Site investigator anticipates that a fully active alternative ART regimen could be constructed in the event of virologic failure on the current ART regimen.The current regimen should have no changes within 4 weeks of enrollment. Subjects must be willing to continue on current antiretroviral therapy for the duration of the study except for the duration of the 16 week analytical treatment interruption. (NOTE: changes to safely begin the treatment interruption are permitted).
- Screening HIV-1 RNA that is ≤50 copies/mL using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent within 30 days prior to enrollment.
Key exclusion criteria (18 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.
- 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 |
|---|---|---|
| Autologous CD4 T-Cellsall participants will receive a single infusion of C34-CXCR4-modified CD4+ T-cells at one of 3 dose levels. The first 3 subjects will receive dose level 1 of 0.8-1x109 transduced CD4+T-cells. Provided no dose limiting toxicity (DLT) is seen at the first dose level, the next 3 subjects will receive infusion at the 2nd dose level of 2.4-3x109 transduced CD4+ T-cells. If no DLT occurs at that dose, the final 3 subjects will receive the 3rd dose level of 0.8-1x1010 transduced CD4+ T-cells. In the event of a DLT (grade 3 or higher unexpected, related AE) recruitment will be paused pending DSMB decision | Biological | Dose level 1:, Dose level 2, Dose level 3 |
Primary outcome
The Number of Subjects With Treatment Related Adverse Events
Time frame: one year
assessed by DAIDS AE grading table v2.0 November 2014
4 secondary outcomes
Compare the Percentage of Enriched Modified Cells C34-CXCR4 Modifiec T- Cells
Time frame: 2 weeks post infusion, prior to ARV reinitiation, weeks 12, 16 and 20
Compare the Change Between CD4 Count
Time frame: Baseline, week 2 post infusion, prior to ARV initiation, weeks 12, 16 20
Compare Viral Set Point Log 10 HIV RNA Level
Time frame: week 2 post infusion, prior to ARV initiation, week 12, 16, 20
Evaluate Cell Mediated Response (Immunogenicity) Using Flow Cytometry
Time frame: baseline through 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Pablo Tebas, MD principal investigator
University of Pennaylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Autologous CD4 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 21 inclusion and 18 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 15 Nov 2022. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Number of Subjects With Treatment Related Adverse Events (time frame: one year). 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 15 Nov 2022.