NCT01734850

Safety Study of a Dual Anti-HIV Gene Transfer Construct to Treat HIV-1 Infection

An Adaptive Phase I/II Study of the Safety of CD4+ T Lymphocytes and CD34+ Hematopoietic Stem/Progenitor Cells Transduced With LVsh5/C46, a Dual Anti-HIV Gene Transfer Construct, With and Without Conditioning With Busulfan in HIV-1 Infected Adults Previously Exposed to ART

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Calimmune, Inc. · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This is an early phase research study looking at whether an experimental gene transfer, LVsh5/C46 (also known as Cal-1), is safe and if it can protect the immune system from the effects of HIV without the use of antiretroviral drugs. Cal-1 is an experimental gene transfer agent designed to inhibit HIV infection through 2 active parts: 1. Removing a protein named CCR5 from bone marrow and white blood cells 2. Producing a protein named C46 on bone marrow and white blood cells

Detailed description

It is estimated that 33 million individuals are currently infected with HIV. HIV/AIDS is a disease that impairs immune function, primarily by decreasing CD4+ T lymphocytes. The progression can be contained by daily dosing with antiretroviral therapy (ART) but there are side effects that can be treatment limiting, and the development of HIV drug resistance can force the physician to modify the ART regimen. There are no effective vaccines currently available for HIV. LVsh5/C46 (also known as Cal-1) is a dual therapeutic, self-inactivating lentiviral vector that encodes for both a short hairpin RNA against the HIV-1 co-receptor CCR5 (sh5) and a HIV-1 fusion inhibitor, C46 and inhibits two processes required for HIV-1 infection: 1. Binding of the virus to the cellular CCR5 co-receptor and 2. Fusion of the virus with the host cell The rationale is that Cal-1 introduced into hematopoietic progenitor/stem cells (HSPC) and mature CD4+ T lymphocytes will protect these cells and their progeny cells from HIV-1 infection and its pathogenic sequelae. This may provide a continuous means of controlling HIV-1 after a single or infrequent dose(s), thereby decreasing or delaying (partially or completely) the need for antiretroviral drug therapy.

Conditions

• Human Immunodeficiency Virus

Interventions

Type	Name	Description
DRUG	Busulfan	Intravenous busulfan
BIOLOGICAL	Cal-1 modified HSPC	Hematopoietic progenitor/stem cells (HSPC) modified with LVsh5/C46 (Cal-1)
BIOLOGICAL	Cal-1 modified CD4+ T lymphocytes	CD4+ T lymphocytes modified with LVsh5/C46 (Cal-1)

Timeline

• Start date: 2013-04-01
• Primary completion: 2017-09-01
• Completion: 2017-11-01
• First posted: 2012-11-28
• Last updated: 2020-08-06
• Results posted: 2020-08-06

Locations

2 sites across 1 country: United States