Trial reportThe Journal of rheumatology2010
Safety, tolerability, and clinical outcomes after intraarticular injection of a recombinant adeno-associated vector containing a tumor necrosis factor antagonist gene: results of a phase 1/2 Study.
Trial report in The Journal of rheumatology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 110 citations in OpenAlex.
- Exosomes from mesenchymal stem/stromal cells and their therapeutic role in osteoarthritic pain.Journal of experimental orthopaedics · 2026Article
- Development of AAV-Mediated Gene Therapy Approaches to Treat Skeletal Diseases.Human gene therapy · 2024Review
- Prevalence of AAV2.5 neutralizing antibodies in synovial fluid and serum of patients with osteoarthritis.Gene therapy · 2023Article
- Retention of peptide-based vesicles in murine knee joints after intra-articular injection.Journal of drug delivery science and technology · 2022Article
- Transduction of Brain Neurons in Juvenile Chum Salmon (International journal of molecular sciences · 2022Article
- Orthopaedic Gene Therapy: Twenty-Five Years On.JBJS reviews · 2021Article
- Update on Novel Non-Operative Treatment for Osteoarthritis: Current Status and Future Trends.Frontiers in pharmacology · 2021Review
- Cellular and Tissue Selectivity of AAV Serotypes for Gene Delivery to Chondrocytes and Cartilage.International journal of medical sciences · 2021Article
- Vasoinhibin reduces joint inflammation, bone loss, and the angiogenesis and vasopermeability of the pannus in murine antigen-induced arthritis.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Article
- The vicissitudes of gene therapy.Bone & joint research · 2019Article
- Bioactive factors for cartilage repair and regeneration: Improving delivery, retention, and activity.Acta biomaterialia · 2019Review
- Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model.Human gene therapy. Clinical development · 2018Article
- Gene Delivery to Joints by Intra-Articular Injection.Human gene therapy · 2018Review
- The silencing of cathepsin K used in gene therapy for periodontal disease reveals the role of cathepsin K in chronic infection and inflammation.Journal of periodontal research · 2016Article
- Preclinical safety evaluation of recombinant adeno-associated virus 2 vector encoding human tumor necrosis factor receptor-immunoglobulin Fc fusion gene.Human vaccines & immunotherapeutics · 2016Article
- scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy.Gene therapy · 2015Article
- Systemic gene transfer of binding immunoglobulin protein (BiP) prevents disease progression in murine collagen-induced arthritis.Clinical and experimental immunology · 2015Article
- Nanomedicine delivers promising treatments for rheumatoid arthritis.Nanomedicine (London, England) · 2015Review
- Use of tissue engineering strategies to repair joint tissues in osteoarthritis: viral gene transfer approaches.Current rheumatology reports · 2014Review
Corrections and comments
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Authors and funding
23 authors at 13 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo assess safety and clinical outcomes in patients with inflammatory arthritis after intraarticular (IA) injection of rAAV2-TNFR:Fc, a recombinant adeno-associated viral vector containing the human tumor necrosis factor (TNF) receptor-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) gene.
methodsIn this phase 1/2 randomized study, adults with persistent moderate or severe inflammation in a target joint, being treated with or without systemic anti-TNF therapy, received a single IA injection of either rAAV2-TNFR:Fc (1 x 10(11), 1 x 10(12), or 1 x 10(13) DNase-resistant particles/ml joint volume) or placebo, followed by open-label rAAV2-TNFR:Fc 12-30 weeks later, depending on when the target joint met predetermined criteria for reinjection.
results127 subjects received the first injection of blinded study drug; 95 subjects received open-label rAAV2-TNFR:Fc. Administration site reactions, consisting of transient mild to moderate increases in tenderness and swelling of the injected joint, occurred after 23/191 (12%) rAAV2-TNFR:Fc injections and were dose-dependent. Rates of other adverse events were not dose-dependent. Notable serious adverse events (SAE) included culture-negative septic arthritis in a subject receiving leflunomide and fatal disseminated histoplasmosis considered unrelated to rAAV2-TNFR:Fc in a subject receiving adalimumab. In the phase 2 portion of the study, a 30% decrease in target joint global visual analog scale was observed in 21/50 (42%) rAAV2-TNFR:Fc subjects and 3/16 (19%) placebo subjects 12 weeks after first injection (p = 0.14).
conclusionIA rAAV2-TNFR:Fc resulted in administration site reactions after 12% of injections. A fatal SAE, disseminated histoplasmosis, was considered not related to study agent. Patient-reported outcome measures of clinical response showed greater improvement in treated patients than placebo patients.
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