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Human Immunodeficiency Virus (HIV)Phase 1NCT02388594

A Phase I Study of T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-728mR in HIV-Infected Patients

A Phase 1 study testing ZFN Modified CD4+ T Cells and Cyclophosphamide in people with Human Immunodeficiency Virus (HIV), run by University of Pennsylvania at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a triple cohort, open-label pilot study of the safety and antiviral activity of a single infusion of autologous CD4+ T cells genetically modified at the CCR5 gene by Zinc Finger Nucleases SB-728mR (ZFN Modified CD4+ T Cells) using electroporated mRNA with or without the prior administration of two different… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Human Immunodeficiency Virus (HIV)
What is being tested?
ZFN Modified CD4+ T Cells and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
Apr 2015to Mar 2019
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

  • HIV-1 infection, as documented by a rapid HIV test or any FDA-approved HIV-1 Enzyme or Chemiluminescence Immunoassay (E/CIA) test kit and confirmed by Western blot at any time prior to study entry or HIV antigen, plasma HIV-1 RNA, or second antibody test by a method other than rapid HIV and E/CIA. Alternatively, if a rapid HIV test or any FDA-approved HIV-1 Enzyme or Chemiluminescence Immunoassay (E/CIA) test kit is not available, two HIV-1 RNA values ≥ 2000 copies/mL at least 24 hours apart performed by any laboratory that has CLIA certification, or its equivalent, may be used to document infection.
  • CD4+ T cell count of ≥450 cells/mm3 at screen; and a documented CD4 nadir of not lower than 200 cells/mm3.
  • Adequate venous access and no other contraindications for leukapheresis.
  • Laboratory values obtained at screen:
  • Hemoglobin: ≥ 10.0 (males); ≥ 9.5 (females) g/dL
  • Absolute neutrophil count (ANC): ≥ 1000/mm3
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  • Platelet count: ≥ 100,000/mm3
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT): ≤ 2.5 times the upper limit of normal (ULN).
  • Subjects must be willing to comply with study-mandated evaluations; including not changing their antiretroviral regimen (unless medically indicated) for 2 months in step 2 or until undergoing the analytical treatment interruption.
  • Be male or female, 18 years of age and older.
  • Ability and willingness of subject to provide informed consent.
  • Have a Karnofsky Performance Score of 70 or higher.
  • Have no polymorphisms in the CCR5 ZFN target region as determined by Cel I snp assay at screening.
  • Subjects in Cohorts 2 and 3: LVEF > or equal to 40%
  • 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: Subject's ART regimen must be in accordance with the Department of Health and Human Services Document "Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents."
  • HIV-1 RNA undetectable by ultrasensitive assay copies/ml obtained at study screening visit or within 60 days prior to study screening visit performed with an ultrasensitive HIV-1 PCR assay. All subjects must have received at least 18 months of therapy and have HIV-1 RNA <50 copies/mL using a FDA-approved assay for at least 48 weeks prior to enrollment. HIV-1 RNA must be measured at least once in the 24 weeks prior to enrollment and at least 3 days before the screening measure. Single determinations that are between ≥50 and <500copies/mL (i.e., 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.
  • Have a recorded viral load set point

Who cannot join

  • Acute or chronic hepatitis B or hepatitis C infection (as further defined in section 6.3.4 and 6.3.8 of this protocol)
  • 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.
  • Have been previously treated with any HIV experimental vaccine within 6 months prior to screening, 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.
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  • 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 study screening visit. 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, dyprydamole, 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 study screening visit.
  • Asymptomatic baseline serum chemistry elevations in LFTs, bilirubin, lipase 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 study screening visit. 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 screening for the study.
  • 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

Other trials in United States

About this study

Official title: A Phase I Study of T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-728mR in HIV-Infected Patients, With or Without the CCR5 Delta-32 Mutation, Pre-treated With Cyclophosphamide

This is a triple cohort, open-label pilot study of the safety and antiviral activity of a single infusion of autologous CD4+ T cells genetically modified at the CCR5 gene by Zinc Finger Nucleases SB-728mR (ZFN Modified CD4+ T Cells) using electroporated mRNA with or without the prior administration of two different doses of cyclophosphamide.

Being tested
ZFN Modified CD4+ T Cells, Cyclophosphamide
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.

Study groups in NCT02388594
Study groupRoleWhat they receive
ZFN Modified CD4+ T CellExperimentalZFN Modified CD4+ T Cell
Receives: Drug: ZFN Modified CD4+ T Cells
ZFN Modified CD4+ T Cell with CyclophosphamideExperimentalZFN Modified CD4+ T Cell with Cyclophosphamide
Receives: Drug: ZFN Modified CD4+ T Cells; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with adverse events

    Measured: 6 months post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2015 (estimated)
  2. Study startApr 2015
  3. Primary completionSep 2018
  4. Study completionMar 2019

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02388594
Sponsor's protocol ID
SB-728mR
Other IDs
U01AI104400
Status last verified
Apr 2019
First submitted
24 Feb 2015
Last updated
10 Apr 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Tebas P, Jadlowsky JK, Shaw PA, Tian L, Esparza E, Brennan AL, Kim S, Naing SY, Richardson MW, Vogel AN, Maldini CR, Kong H, Liu X, Lacey SF, Bauer AM, Mampe F, Richman LP, Lee G, Ando D, Levine BL, Porter DL, Zhao Y, Siegel DL, Bar KJ, June CH, Riley JL. CCR5-edited CD4+ T cells augment HIV-specific immunity to enable post-rebound control of HIV replication. J Clin Invest. 2021 Apr 1;131(7):e144486. doi: 10.1172/JCI144486.

    PubMed 33571163

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ZFN Modified CD4+ T Cells and Cyclophosphamide in people with Human Immunodeficiency Virus (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 17 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: finished, as of the sponsor's last update on 10 Apr 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?

Number of participants with adverse events (time frame: 6 months post treatment). 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 NCT02388594, 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 10 Apr 2019; AzTrials last refreshed its copy on 6 Nov 2026.

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