Trial of an Anti-HIV-1 Gene Transfer Product - Full Text View

Sponsor:	Janssen-Cilag Pty Ltd
Information provided by:	Janssen-Cilag Pty Ltd
ClinicalTrials.gov Identifier:	NCT00074997

Purpose

The objective of this study is to determine the safety and efficacy of administration of a cell-delivered ribozyme gene transfer product to patients with chronic Human Immunodeficiency Virus Type One (HIV-1) infection.

Condition	Intervention	Phase
HIV-1	Other: Placebo Genetic: OZ1	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Randomized Phase II, Double-Blind, Controlled Trial to Evaluate the Safety and Efficacy of Autologous CD34+ Hematopoietic Progenitor Cells Transduced With Placebo or an Anti-HIV-1 Ribozyme (OZ1) in Patients With HIV-1 Infection

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by Janssen-Cilag Pty Ltd:

Primary Outcome Measures:

Difference in viral load between the placebo and OZ1 groups. [ Time Frame: Week 47 ] [ Designated as safety issue: No ]
Difference in viral load between the placebo and OZ1 groups. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

CD4+ cell count [ Time Frame: Weeks 41 - 48 ] [ Designated as safety issue: No ]
HIV proviral DNA [ Time Frame: Weeks 41 - 48 ] [ Designated as safety issue: No ]
Thymic function [ Time Frame: Weeks 41 - 48 ] [ Designated as safety issue: No ]
Time to resumption of antiretroviral therapy [ Time Frame: Weeks 41 - 48 ] [ Designated as safety issue: No ]

Enrollment:	1
Study Start Date:	July 2002
Study Completion Date:	January 2008
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 001 OZ1 Single intravenous infusion of 2-20 x 10 to the power of 7 OZ1 transduced autologous CD34+ cells per kilogram of body weight	Genetic: OZ1 Single intravenous infusion of 2-20 x 10 to the power of 7 OZ1 transduced autologous CD34+ cells per kilogram of body weight
Placebo Comparator: 002 Placebo Single intravenous infusion of placebo transduced autologous CD34+ cells per kilogram of body weight	Other: Placebo Single intravenous infusion of placebo transduced autologous CD34+ cells per kilogram of body weight

Detailed Description:

This trial uses an experimental approach called "gene transfer". This procedure involves removing some early stage bone marrow cells (known as CD34+ cells) from the blood and inserting a gene into them. The gene produces a molecule known as a ribozyme, which cuts up the genetic material of the Human Immunodeficiency Virus (HIV). The procedure on inserting the ribozyme gene into the CD34+ cells takes place in the laboratory. When the CD34+ cells containing the new gene are put back into the body, they go back to the bone marrow and produce white blood cells such as T-cells, which also contain the new gene. It has been shown in laboratory experiments that the T-cells containing the ribozyme gene have reduced replication of HIV because of the effects of the ribozyme on the virus. The name of the investigational ribozyme gene is OZ1. OZ1 has the potential, after a single administration to reduce the amount of HIV in the body and improve the function of the immune system by increasing the number of T-cells. The purpose of the trial is to determine if the insertion of OZ1 into CD34+ cells is safe and if it reduces HIV replication in the body and increases the number of T-cells in comparison to CD34+ cells alone. Patients will be divided into two groups: one group will receive OZ1-containing CD34+ cells, the other group will receive CD34+ cells alone. A series of procedures will be conducted to harvest CD34+ cells from the blood. At the completion of these procedures the white blood cells will be transferred to a laboratory where they are purified to isolate the CD34+ cells. The cells will then undergo one of two possible procedures: culture of the cells and insertion of OZ1 or culture of the cells only. Once this procedure is complete, the cells will be returned to the patient via an infusion. The infusion is a one-off treatment.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Human Immunodeficiency Virus -1 (HIV-1) infection for at least 6 months documented by positive HIV serology
Receiving either the first or second regimen of antiretroviral therapy (ART) defined as 3 or more antiretroviral drugs in combination
Viral load less than 400 copies/ml
CD4+ cell count must be greater that 300 cells/mm3

Exclusion Criteria:

Any previous or current Acquired Immunodeficiency Syndrome (AIDS) defining illness by the CDC case definition, including AIDS-related dementia, with the exception of Kaposi's sarcoma
Clinically significant clinical laboratory results
Patients with veins unsuitable for study related procedures
Currently pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074997

Sponsors and Collaborators

Janssen-Cilag Pty Ltd

Investigators

Study Director:

Janssen-Cilag Pty Ltd Clinical Trial

Janssen-Cilag Pty Ltd

More Information

No publications provided by Janssen-Cilag Pty Ltd

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mitsuyasu RT, Merigan TC, Carr A, Zack JA, Winters MA, Workman C, Bloch M, Lalezari J, Becker S, Thornton L, Akil B, Khanlou H, Finlayson R, McFarlane R, Smith DE, Garsia R, Ma D, Law M, Murray JM, von Kalle C, Ely JA, Patino SM, Knop AE, Wong P, Todd AV, Haughton M, Fuery C, Macpherson JL, Symonds GP, Evans LA, Pond SM, Cooper DA. Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells. Nat Med. 2009 Mar;15(3):285-92. Epub 2009 Feb 15.

Responsible Party:	Executive Director Medical & Scientific Affairs, Janssen-Cilag Pty Ltd, Australia
ClinicalTrials.gov Identifier:	NCT00074997 History of Changes
Other Study ID Numbers:	CR010783, OZ1-HV1-201, OTH/OZ1-INT-1
Study First Received:	December 28, 2003
Last Updated:	August 27, 2010
Health Authority:	United States: Food and Drug Administration; Australia: Department of Health

Keywords provided by Janssen-Cilag Pty Ltd:

Gene Therapy
Anti-HIV-1 Ribozyme
OZ1
HIV-1 Infections

ClinicalTrials.gov processed this record on February 12, 2012