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NCT01177059

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

Completed Phase 2 Results posted Last updated 12 December 2018
What this trial tests

Phase 2 trial testing OZ1 transduced cells in HIV-1 in 68 participants. Completed in 30 November 2017.

Timeline
6 December 2004
Primary endpoint
30 November 2017
30 November 2017

Quick facts

Lead sponsorJanssen-Cilag Pty Ltd
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposeother
Enrollment68
Start date6 December 2004
Primary completion30 November 2017
Estimated completion30 November 2017
Sites6 locations across United States, Australia

Drugs / interventions tested

Conditions studied

Sponsor

Janssen-Cilag Pty Ltd — full company profile →

Who can join

Eligibility, any sex, with HIV-1. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Clonal Expansion of Cells With a Predominant OZ1 Insertion Site Primary · Approximately up to 15 years

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.

GroupValue95% CI
Anti-HIV-1 Ribozyme (OZ1) Transduced Cells0
Percentage of Participants With Insertional Oncogenesis Primary · Approximately up to 15 years

Percentage of participants with insertional oncogenesis by clonal expansion of cells modified with OZ1/LNL6 were reported.

GroupValue95% CI
Anti-HIV-1 Ribozyme (OZ1) Transduced Cells0
Number of Participants With Quantitative Marking of Gene Transfer Product in Peripheral Blood Mononuclear Cells (PBMC) Over Time Primary · Up to end of study (Approximately up to 15 years)

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.

2 years post-infusion: Not Detected
GroupValue95% CI
Anti-HIV-1 Ribozyme (OZ1) Transduced Cells33
2 years post-infusion: 1/3 Detected
GroupValue95% CI
Anti-HIV-1 Ribozyme (OZ1) Transduced Cells4
2 years post-infusion: 2/3 Detected
GroupValue95% CI
Anti-HIV-1 Ribozyme (OZ1) Transduced Cells0
2 years post-infusion: 3/3 Detected
GroupValue95% CI
Anti-HIV-1 Ribozyme (OZ1) Transduced Cells0
2 years post-infusion: Detected (Quantifiable)
GroupValue95% CI
Anti-HIV-1 Ribozyme (OZ1) Transduced Cells0
2.5 years post-infusion: Not Detected
GroupValue95% CI
Anti-HIV-1 Ribozyme (OZ1) Transduced Cells31
2.5 years post-infusion: 1/3 Detected
GroupValue95% CI
Anti-HIV-1 Ribozyme (OZ1) Transduced Cells2
2.5 years post-infusion: 2/3 Detected
GroupValue95% CI
Anti-HIV-1 Ribozyme (OZ1) Transduced Cells1

Adverse events — posted to ClinicalTrials.gov

Time frame: Approximately up to 15 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Anti-HIV-1 Ribozyme (OZ1) Transduced Cells
Serious: 7/68 (10%)
Deaths: 0/68

Serious adverse events (11 terms)

ReactionSystemAnti-HIV-1 Ribozyme (OZ1) …
Rib FractureInjury, poisoning and procedural complications
Basal Cell CarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's DiseaseNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Kaposi's SarcomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary Thyroid CancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin CancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Testicle AdenomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Premature BabyPregnancy, puerperium and perinatal conditions
Suicidal IdeationPsychiatric disorders
Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders
Deep Vein ThrombosisVascular disorders
Other adverse events (1 terms — click to expand)

ReactionSystemAnti-HIV-1 Ribozyme (OZ1) …
HypertensionVascular disorders

Most-reported serious reactions: Rib Fracture, Basal Cell Carcinoma, Hodgkin's Disease, Kaposi's Sarcoma, Papillary Thyroid Cancer, Skin Cancer, Testicle Adenoma, Premature Baby.

Data from ClinicalTrials.gov NCT01177059 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.
    Yu AM, Choi YH, Tu MJ. · · 2020 · cited 271× · PMID 32929000 · DOI 10.1124/pr.120.019554
  2. HIV-specific Immunity Derived From Chimeric Antigen Receptor-engineered Stem Cells.
    Zhen A, Kamata M, Rezek V, Rick J, et al · · 2015 · cited 120× · PMID 26050990 · DOI 10.1038/mt.2015.102
  3. Improved Nucleic Acid Therapy with Advanced Nanoscale Biotechnology.
    Weng Y, Huang Q, Li C, Yang Y, et al · · 2020 · cited 72× · PMID 31927331 · DOI 10.1016/j.omtn.2019.12.004
  4. RNA interference approaches for treatment of HIV-1 infection.
    Bobbin ML, Burnett JC, Rossi JJ. · · 2015 · cited 61× · PMID 26019725 · DOI 10.1186/s13073-015-0174-y
  5. Creating genetic resistance to HIV.
    Burnett JC, Zaia JA, Rossi JJ. · · 2012 · cited 30× · PMID 22985479 · DOI 10.1016/j.coi.2012.08.013
  6. The therapeutic landscape of HIV-1 via genome editing.
    Kwarteng A, Ahuno ST, Kwakye-Nuako G. · · 2017 · cited 16× · PMID 28705213 · DOI 10.1186/s12981-017-0157-8
  7. Bone Marrow Gene Therapy for HIV/AIDS.
    Herrera-Carrillo E, Berkhout B. · · 2015 · cited 15× · PMID 26193303 · DOI 10.3390/v7072804
  8. Advances in HIV Gene Therapy.
    Kitawi R, Ledger S, Kelleher AD, Ahlenstiel CL. · · 2024 · cited 11× · PMID 38474018 · DOI 10.3390/ijms25052771

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