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

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

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.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus (HIV)
• Intervention / Treatment: Genetic: SB-728mR-T; Genetic: SB-728mR-T; Drug: Cyclophosphamide

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
  • Connecticut
    • Norwalk, Connecticut, United States, 06850
  • Florida
    • Orlando, Florida, United States, 32803
  • Texas
    • Austin, Texas, United States, 78705
    • Dallas, Texas, United States, 75246

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	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); Genetic: 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
Experimental: Cohort 2	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); Genetic: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measure	Effect of SB-728mR-T on plasma HIV-1 RNA levels following HAART interruption	12 months
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

Collaborators and Investigators

• Sponsor: Sangamo Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: August 22, 2014
• First Submitted That Met QC Criteria: August 22, 2014
• First Posted (Estimate): August 26, 2014

Study Record Updates

• Last Update Posted (Actual): March 19, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: SB-728mR-1401