Repeat Doses of SB-728mR-T After Cyclophosphamide Conditioning in HIV-Infected Subjects on HAART

Human Immunodeficiency Virus (HIV) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02225665
• Other study ID #: SB-728mR-1401
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 2014
• Est. completion date: June 2018

Study information

• Verified date: December 2020
• Source: Sangamo Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus (HIV)

Intervention

Genetic:
• SB-728mR-T
-SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)
• SB-728mR-T
- SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)

Drug:
• Cyclophosphamide
- IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sangamo Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Outcome Measure	Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728mR-T infusion	12 months
Secondary	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.	12 months
Secondary	Secondary Outcome Measure	Effect of SB-728mR-T on plasma HIV-1 RNA levels following HAART interruption	12 months
Secondary	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)	Baseline and 12 months