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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag Pty Ltd
ClinicalTrials.gov Identifier:
NCT00074997
First received: December 28, 2003
Last updated: June 17, 2016
Last verified: June 2016
  Purpose
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 Intervention Phase
HIV-1
Other: Placebo
Genetic: OZ1
Genetic: CD34+ cells
Phase 2

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:


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: December 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 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.

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.
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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):
Responsible Party: Janssen-Cilag Pty Ltd
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: June 17, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Australia: Human Research Ethics Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Janssen-Cilag Pty Ltd:
Gene Therapy
Anti-HIV-1 Ribozyme
OZ1
HIV-1 Infections

Additional relevant MeSH terms:
Infection

ClinicalTrials.gov processed this record on July 28, 2016