Status:
COMPLETED
Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-728 for HIV
Lead Sponsor:
University of Pennsylvania
Collaborating Sponsors:
Sangamo Therapeutics
Conditions:
HIV
HIV Infections
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief 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 nam...
Detailed Description
Cohort 1 - Patients who have failed two more HAART regimens (6 subjects) Cohort 2 - Patients doing well on a stable antiretroviral medication (6 subjects) Cohort 3 - Patients who have an undetectabl...
Eligibility Criteria
Inclusion
- Cohort 1 Only:
- Patients who have been on two more HAART regimens and have failed due to resistance or tolerance (no changes to treatment within 4 weeks of study entry), and who have no viable treatment options likely to result in complete viral suppression.
- CD4+ T cell count of ≥200 cells/mm3
- HIV-1 RNA ≥2000 copies/mL obtained within 60 days prior to study entry performed with an ultrasensitive HIV-1 PCR assay.
- Two HIV-1 RNA levels \<150,000 copies/mL obtained within 60 days prior to study entry performed with an ultrasensitive HIV-1 PCR assay. These HIV-1 RNA measurements must be at least 48 hours apart and may include the HIV-1 RNA measurement done at the time of the screening visit.
- Ongoing treatment with HIV entry inhibitors such as enfurvitide or maraviroc are excluded
- Cohort 2 Only:
- On a stable antiretroviral medication (no changes to treatment within 4 weeks of study entry) and be willing to continue on current antiretroviral therapy for the duration of the study until undergoing structured treatment interruption.
- CD4+ T cell count of ≥450 cells/mm3 at screen; and a documented CD4 nadir of not lower than 300 cells/mm.
- HIV-1 RNA undetectable by ultrasensitive HIV PCR assay obtained within 60 days prior to study entry performed with an ultrasensitive HIV-1 PCR assay.
- Cohort 3 only:
- On a stable antiretroviral medication (no changes to treatment within 4 weeks of study entry) and be willing to continue on current antiretroviral therapy for the duration of the study.
- CD4+ T cell count that is persistently \<500 cells/mm3 despite at least 2 years of stable HAART and \>200 cells/mm3 at screen
- Subjects must have received at least 2 continuous years of therapy and have had undetectable viral loads by ultrasensitive assay since 6 months of therapy. Subjects who have had a single viral load blip at any point in this time, or who experience intermittent isolated episodes of detectable low-level viremia (detectable but \<1000 copies RNA/mL; blips) will remain eligible.
- Subjects who are currently taking maraviroc or have received maraviroc within 6 months of study entry are excluded.
- Inclusion for Cohort 1, Cohort 2, Cohort 3:
- HIV-1 infection, as documented by ELISA and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
- 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 Platelet count: ≥ 100,000/mm3 Serum creatinine: ≤ 1.5 mg/dL (133µ mol/L) 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 (Cohort 1) or until undergoing structured treatment interruption (Cohort 2).
- Karnofsky Performance Score of 70 or higher
Exclusion
- Acute or chronic hepatitis B or hepatitis C infection
- Current or prior AIDS diagnosis (Cohort 1 and 2 only)
- History of cancer or malignancy, (basal cell or squamous cell carcinoma of the skin allowed)
- History or problems with uncontrolled heart disease, bleeding or hemodynamic instability.
- Have been previously treated with any HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector.
- Use of the following medications within the last 30 days: chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.)
- Breast-feeding, pregnant, or unwilling to use acceptable methods of birth control.
- 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 investigator, would interfere with adherence to study requirements
- 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 an allergy or hypersensitivity to study product excipients (human serum albumin, DMSO and Dextran 40).
- Currently taking medications called HIV entry inhibitors such as enfuvirtide or maraviroc
Key Trial Info
Start Date :
January 1 2009
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 1 2013
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT00842634
Start Date
January 1 2009
End Date
January 1 2013
Last Update
February 8 2019
Active Locations (2)
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1
Jacobi Medical Cener
The Bronx, New York, United States, 10461
2
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104