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

University of Pennsylvania1 site in 1 country14 target enrollmentApril 2015

ConditionsHuman Immunodeficiency Virus (HIV)

InterventionsZFN Modified CD4+ T Cells Cyclophosphamide

DrugsZFN Modified CD4+ T Cells Cyclophosphamide

Overview

Phase: Phase 1
Intervention: ZFN Modified CD4+ T Cells
Conditions: Human Immunodeficiency Virus (HIV)
Sponsor: University of Pennsylvania
Enrollment: 14
Locations: 1
Primary Endpoint: Number of participants with adverse events
Status: Completed
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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 doses of cyclophosphamide.

Registry

clinicaltrials.gov

Start Date

April 2015

End Date

March 2019

Last Updated

7 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University of Pennsylvania

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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/mm
•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
•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.

Exclusion Criteria

•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.
•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.