Long Term Follow-Up Study of Human Immunodeficiency Virus Type 1 (HIV-1) Positive Patients Who Have Received OZ1 Gene Therapy as Part of a Clinical Trial

A Long Term Follow-up Protocol to Evaluate the Safety and Survival of Autologous CD34+ Hematopoietic Progenitor Cells Transduced With an Anti-HIV-1 Ribozyme (OZ1) in Patients With HIV-1 Infection

The purpose of this Observational Study is long term follow-up of the Human Immunodeficiency Virus -1 (HIV-1) infected patients who have received a gene therapy product (anti-HIV-1 Ribozyme [OZ1]) as part of an earlier phase 2 trial. Patients are seen twice yearly until 5 years from initial infusion of study drug has elapsed and then yearly until withdrawal or study completion. The study will monitor for and record any ill effects from the gene therapy product to provide long term safety information.

Study Overview

• Status: Completed
• Conditions: HIV-1
• Intervention / Treatment: Genetic: OZ1 transduced cells

Detailed Description

During an earlier phase 2 base trial (study # NCT00074997), HIV-1 infected patients received a gene therapy product (anti-HIV-1 Ribozyme [OZ1]). Gene therapy is an investigational treatment where genes are inserted into an individual's cells and tissues to treat a disease. The gene therapy OZ1 is thought to have anti-HIV-1 actions. This is an Observational Study to provide long term follow-up of those HIV-1 infected patients who received the gene therapy product (anti-HIV-1 Ribozyme [OZ1]) as part of the earlier study. Patients are seen twice yearly until 5 years from initial infusion of study drug has elapsed and then yearly until withdrawal or study completion. The study will monitor for and record any ill effects from the gene therapy product to provide long term safety information. Observational study - no investigational drug administered.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Darlinghurst, Australia
  • Surry Hills, Australia
  • Sydney, Australia
• United States
  • California
    • Los Angeles, California, United States
    • San Francisco, California, United States
  • New York
    • New York, New York, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients who were enrolled (between 18 and 45 years of age) in the base study "OTH/OZ1-INT-1" (NCT00074997) will be invited to participate in this long term follow-up study
• Patients must have received the Final Cell Product infusion in base study "OTH/OZ1-INT-1"
• Have signed Informed Consent Form

Exclusion Criteria:

• All patients who were enrolled in the OTH/OZ1-INT-1 study and received the final cell product will be invited to participate in this long term follow-up study. After unblinding of the OTH/OZ1-INT-1 study, any patients in the placebo arm will be withdrawn from this protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Anti-HIV-1 Ribozyme (OZ1) transduced cells; OZ1 transduced cells Long term follow up of previously infused OZ1 transduced cells	Genetic: OZ1 transduced cells; Long term follow up of previously infused OZ1 transduced cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clonal Expansion of Cells With a Predominant OZ1 Insertion Site	Percentage of participants with clonal expansion of cells with a predominant OZ1 insertion site was reported. A predominant integration site was defined as an integration site which has a density of at least 50 percent (%) of the total signal detected by polymerase chain reaction (PCR), when the percentage of cells marked by vector was greater than (>)1% of the test cell population.	Approximately up to 15 years
Percentage of Participants With Insertional Oncogenesis	Percentage of participants with insertional oncogenesis by clonal expansion of cells modified with OZ1/LNL6 were reported.	Approximately up to 15 years
Number of Participants With Quantitative Marking of Gene Transfer Product in Peripheral Blood Mononuclear Cells (PBMC) Over Time	OZ1 and LNL6 marking analysis were performed by quantitative deoxyribonucleic acid-polymerase chain reaction (DNA-PCR). Number of participants in each of 3 categories for gene detection: Not Detected, Detected (1, 2 and 3 of the 3 triplicates of the sample were detected respectively [1/3 Detected, 2/3 Detected, 3/3 Detected]) and Detected (Quantifiable) were reported for marking of gene transfer product in PBMC.	Up to end of study (Approximately up to 15 years)

Collaborators and Investigators

• Sponsor: Janssen-Cilag Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2004
• Primary Completion (Actual): November 30, 2017
• Study Completion (Actual): November 30, 2017

Study Registration Dates

• First Submitted: August 5, 2010
• First Submitted That Met QC Criteria: August 5, 2010
• First Posted (Estimate): August 6, 2010

Study Record Updates

• Last Update Posted (Actual): December 12, 2018
• Last Update Submitted That Met QC Criteria: November 20, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Gene Therapy; HIV-1 Infections; Anti-HIV-1 Ribozyme; OZ1
• Other Study ID Numbers: CR016027; OZ1-HV1-202 (Other Identifier: Janssen-Cilag Pty Ltd, Australia)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No