Back to resultsRepeat Doses of SB-728mR-T After Cyclophosphamide Conditioning in HIV-Infected Subjects on HAART
Primary Purpose
Human Immunodeficiency Virus (HIV)
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SB-728mR-T
SB-728mR-T
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus (HIV)
Eligibility Criteria
Inclusion Criteria:
- Male or female, 18 years of age or older with documented HIV diagnosis.
- Must be willing to comply with study-mandated evaluations; including discontinuation of current antiretroviral therapy during the treatment interruption.
- Initiated HAART therapy within (≤) 1 year of HIV diagnosis or suspected infection.
- Undetectable HIV-1 RNA for at least 2 months prior to screening and at screening.
- CD4+ T-cell count ≥500 cells/µL.
- Absolute neutrophil count (ANC) ≥ 2500/mm3.
- Platelet count ≥ 200,000/mm3.
Exclusion Criteria:
- Acute or chronic hepatitis B or hepatitis C infection.
- Active or recent (in prior 6 months) AIDS defining complication.
- Any cancer or malignancy within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal or cervical dysplasia.
- Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or uncontrolled arrhythmias.
- History or any features on physical examination indicative of a bleeding diathesis.
- Received HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector.
- Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents within 30 days prior to screening.
- 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.
- Currently participating in another clinical trial or participation in such a trial within 30 days prior to screening visit.
- Currently taking maraviroc or have received maraviroc within 6 months prior to screening.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
Outcomes
Primary Outcome Measures
Primary Outcome Measure
Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728mR-T infusion
Secondary Outcome Measures
Secondary Outcome Measure
Effect of repeat doses of SB-728mR-T on engraftment following cyclophosphamide conditioning as measured by CCR5 Modified CD4 Cells at Month 12.
Secondary Outcome Measure
Effect of SB-728mR-T on plasma HIV-1 RNA levels following HAART interruption
Secondary Outcome Measure
Change from baseline to month 12 in CD4+ T-cell counts in peripheral blood after repeat treatments with SB-728mR-T. (i.e. month 12 value - baseline value)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02225665
Brief Title
Repeat Doses of SB-728mR-T After Cyclophosphamide Conditioning in HIV-Infected Subjects on HAART
Official Title
A Phase 1/2, Open-Label Study to Assess the Safety and Tolerability of Repeat Doses of Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Subjects Following Cyclophosphamide Conditioning
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
August 2014 (Actual)
Primary Completion Date
June 2018 (Actual)
Study Completion Date
June 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sangamo Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of repeat doses of T-cell immunotherapy (SB-728mR-T) following cyclophosphamide conditioning.
CCR5 is a major co-receptor for HIV entry into T-cells. Disruption of CCR5 by zinc finger nuclease (SB-728mR), blocks HIV entry into the T-cells, therefore, protects the T-cells from HIV infection. Safety (primary outcome) and anti-viral effect (secondary outcome) of zinc finger nuclease-mediated CCR5 disrupted autologous T-cells (SB-728mR-T) will be evaluated in the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus (HIV)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Title
Cohort 2
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
SB-728mR-T
Intervention Description
-SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)
Intervention Type
Genetic
Intervention Name(s)
SB-728mR-T
Intervention Description
- SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
- IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion
Primary Outcome Measure Information:
Title
Primary Outcome Measure
Description
Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728mR-T infusion
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Secondary Outcome Measure
Description
Effect of repeat doses of SB-728mR-T on engraftment following cyclophosphamide conditioning as measured by CCR5 Modified CD4 Cells at Month 12.
Time Frame
12 months
Title
Secondary Outcome Measure
Description
Effect of SB-728mR-T on plasma HIV-1 RNA levels following HAART interruption
Time Frame
12 months
Title
Secondary Outcome Measure
Description
Change from baseline to month 12 in CD4+ T-cell counts in peripheral blood after repeat treatments with SB-728mR-T. (i.e. month 12 value - baseline value)
Time Frame
Baseline and 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, 18 years of age or older with documented HIV diagnosis.
Must be willing to comply with study-mandated evaluations; including discontinuation of current antiretroviral therapy during the treatment interruption.
Initiated HAART therapy within (≤) 1 year of HIV diagnosis or suspected infection.
Undetectable HIV-1 RNA for at least 2 months prior to screening and at screening.
CD4+ T-cell count ≥500 cells/µL.
Absolute neutrophil count (ANC) ≥ 2500/mm3.
Platelet count ≥ 200,000/mm3.
Exclusion Criteria:
Acute or chronic hepatitis B or hepatitis C infection.
Active or recent (in prior 6 months) AIDS defining complication.
Any cancer or malignancy within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal or cervical dysplasia.
Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or uncontrolled arrhythmias.
History or any features on physical examination indicative of a bleeding diathesis.
Received HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector.
Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents within 30 days prior to screening.
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.
Currently participating in another clinical trial or participation in such a trial within 30 days prior to screening visit.
Currently taking maraviroc or have received maraviroc within 6 months prior to screening.
Facility Information:
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
Norwalk
State/Province
Connecticut
ZIP/Postal Code
06850
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Repeat Doses of SB-728mR-T After Cyclophosphamide Conditioning in HIV-Infected Subjects on HAART
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