An Efficacy and Safety Study of Autologous Cluster of Differentiation 34 (CD34+) Hematopoietic Progenitor Cells Transduced With Placebo or an Anti- Human Immunodeficiency Virus Type 1 (HIV-1) Ribozyme (OZ1) in Participants With HIV-1 Infection

• ClinicalTrials.gov Identifier: NCT00074997
• Recruitment Status: Completed
• First Posted: December 31, 2003
• Last Update Posted: June 20, 2016
• Sponsor: Janssen-Cilag Pty Ltd
• Information provided by (Responsible Party): Janssen-Cilag Pty Ltd

Study Description

Brief Summary:

The purpose of this study is to determine the safety and efficacy of administration of a cell-delivered ribozyme gene transfer product to participants with chronic (lasting a long time) Human Immunodeficiency Virus Type 1 (HIV-1) infection (a life-threatening infection which you can get from an infected person's blood or from having sex with an infected person).

Condition or disease	Intervention/treatment	Phase
HIV-1	Other: Placebo; Genetic: OZ1; Genetic: CD34+ cells	Phase 2

Detailed Description:

This is a randomized (study drug assigned by chance), double-blind (neither the participant nor the physician know the study medication drug name), placebo (an inactive substance that is compared with a drug to test if the drug has a real effect in a clinical trial) controlled study to investigate safety and efficacy of administration of autologous cluster of differentiation 34 (CD34+) cells transduced with placebo or an anti-HIV-ribozyme (OZ1) in participants with HIV-1 infection. The total study duration will be 100 weeks and will include following visits: screening, pre-infusion Days 1-7, Day 8, Week 1, 4, 8, 12, 16, 20, 24, 25, 26, 27, 28, 30, 32, 34, 36, 38, 40, 41, 42, 43, 44, 45, 46, 47, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 and 100. Before the administration of CD34+ final cell product, a number of procedures will be performed, including the injection of granulocyte colony-stimulating factor (G-CSF) to mobilize the CD34+ cells, apheresis and the transduction of the CD34+ cells with either OZ1 or placebo. Participants will be divided into two groups: one group will receive OZ1-containing CD34+ cells, the other group will receive CD34+ cells alone and will receive a single intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) of CD34+ cells transduced with either placebo or OZ1 gene transfer product. The final cell product contains approximately 2-20 x 10^7 cells/kilogram autologous CD34+ cell suspension transduced with either placebo or OZ1 gene transfer product. Primary efficacy will be assessed primarily by the amount of HIV ribonucleic acid (RNA) (viral load). Participants' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Study Start Date: December 2002
• Actual Primary Completion Date: January 2008
• Actual Study Completion Date: January 2008

Arms and Interventions

Arm	Intervention/treatment
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 OZ1.; Genetic: CD34+ cells; Autologous CD34+ cells.
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.; Genetic: CD34+ cells; Autologous CD34+ cells.

Outcome Measures

Primary Outcome Measures :

1. Difference in viral load between the placebo and OZ1 groups. [ Time Frame: Week 47 ]
2. Difference in viral load between the placebo and OZ1 groups. [ Time Frame: Week 48 ]

Secondary Outcome Measures :

1. CD4+ cell count [ Time Frame: Weeks 41 - 48 ]
2. HIV proviral DNA [ Time Frame: Weeks 41 - 48 ]
3. Thymic function [ Time Frame: Weeks 41 - 48 ]
4. Time to resumption of antiretroviral therapy [ Time Frame: Weeks 41 - 48 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• An Human Immunodeficiency Virus 1 (HIV-1) infection for at least 6 months documented by positive HIV serology including confirmation by Western Blot
• Receiving either the first or second regimen of antiretroviral therapy (ART) defined as 3 or more antiretroviral drugs in combination
• A Viral load less than 400 copies per milliliter (copies/ml), as measured by Roche Amplicor HIV-1 Monitor assay, on 2 consecutive occasions, at least 7 days apart and within 45 days prior to granulocyte colony-stimulating factor (G-CSF) administration and the second measurement has to be within 14 days prior to G-CSF
• Cluster of Differentiation 4 (CD4+) cell count must be greater that 300 cells per cubic millimeter (cells/mm^3)
• Women and men (or their partners) had to agree to use a medically accepted form of contraception and safe sexual practices

Exclusion Criteria:

• Any previous or current Acquired Immunodeficiency Syndrome (AIDS) defining illness by the Center for Disease Control (CDC) case definition, including AIDS-related dementia (mental decline), with the exception of Kaposi's sarcoma (purple or brown cancerous pimples on the skin, often associated with AIDS)
• Clinically significant clinical laboratory results
• Participants with veins unsuitable for study related procedures
• Current ART that included antiretroviral agents which exhibited antagonism when used together (example, zidovudine and stavudine ), or current or previous ART that included hydroxyurea
• Current pregnancy or breastfeeding

Contacts and Locations

Locations

Australia

Darlinghurst, Australia

Sponsors and Collaborators

Janssen-Cilag Pty Ltd

Investigators

• Study Director: Janssen-Cilag Pty Ltd Clinical Trial; Janssen-Cilag Pty Ltd

More Information

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. doi: 10.1038/nm.1932. Epub 2009 Feb 15.

• Responsible Party: Janssen-Cilag Pty Ltd
• ClinicalTrials.gov Identifier: NCT00074997
• Other Study ID Numbers: CR010783; OZ1-HV1-201; OTH/OZ1-INT-1
• First Posted: December 31, 2003
• Last Update Posted: June 20, 2016
• Last Verified: June 2016

Keywords provided by Janssen-Cilag Pty Ltd:

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

Additional relevant MeSH terms:

Infection