A Phase I/II Study of Repeat Intra-articular Administration of tgAAC94, a Recombinant Adeno-Associated Vector Containing the TNFR:Fc Fusion Gene, in Inflammatory Arthritis Subjects With and Without Concurrent TNF-alpha Antagonists

The 13G01 clinical trial is a Phase I/II dose escalation study designed to be conducted in adults with inflammatory arthritis who have persistent moderate or severe swelling in one or more joints, without a disease severe enough to warrant a change in regimen for the next three months.
The study will permit subjects who are concurrently on anti-tumor necrosis factor (TNF)-alpha antagonists. For subjects on disease modifying antirheumatic drugs (DMARDs), a stable regimen for inflammatory arthritis for the previous three months, with no changes in doses in the four weeks prior to screening will be required.
The primary objectives are:
1. to evaluate the safety of intra-articular administration of tgAAC94 in subjects currently taking TNF-alpha antagonists, and
2. to evaluate the safety of repeat intra-articular administration of tgAAC94 (gene therapy vector).

Start Date01 Aug 2005

Sponsor / Collaborator

AmpliPhi Biosciences Corp.

NCT00617032

/ CompletedPhase 1

A Phase 1 Dose Escalation Study of Intra-Articular Administration of tgAAC94, a Recombinant Adeno-Associated Vector Containing the TNFR:Fc Fusion Gene, in Inflammatory Arthritis

Study 1304 is a Phase I dose escalation study conducted in adults with persistent moderate (grade 2) or severe (grade 3) swelling due to inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis) in at least one peripheral joint eligible for injection. Disease must not be severe enough to warrant use of a TNF-alpha antagonist in the next three months.
Current use of TNF-alpha antagonists is not permitted. Subjects with rheumatoid arthritis must have had an adequate trial of at least one disease-modifying antirheumatic drug (DMARD) prior to screening.
The primary objective is to evaluate the safety of intra-articular administration of tgAAC94.

Start Date01 Feb 2004

Sponsor / Collaborator

AmpliPhi Biosciences Corp.

100 Clinical Results associated with tgAAC 94

100 Translational Medicine associated with tgAAC 94

100 Patents (Medical) associated with tgAAC 94

Literatures (Medical) associated with tgAAC 94

01 Jun 2012·Pain medicine (Malden, Mass.)Q3 · MEDICINE

Evidence-Based Knee Injections for the Management of Arthritis

Q3 · MEDICINE

Review

Author: Olivia T. Cheng, BA ; Dmitri Souzdalnitski, MD ; Bruce Vrooman, MD ; Jianguo Cheng, MD, PhD

OBJECTIVE:

Arthritis of the knee affects 46 million Americans. We aimed to determine the level of evidence of intraarticular knee injections in the management of arthritic knee pain.

METHODS:

We systematically searched PUBMED/MEDLINE and the Cochrane databases for articles published on knee injections and evaluated their level of evidence and recommendations according to established criteria.

RESULTS:

The evidence supports the use of intraarticular corticosteroid injections for rheumatoid arthritis (1A+ Level), osteoarthritis (1A+ Level), and juvenile idiopathic arthritis (2C+ Level). Pain relief and functional improvement are significant for months up to 1 year after the injection. Triamcinolone hexacetonide offers an advantage over triamcinolone acetonide and should be the intraarticular steroid of choice (2B+ Level). Intraarticular injection of hyaluronate may provide longer pain relief than steroid injection in osteoarthritis (2B+ Level). It can also be effective for rheumatoid arthritis knee pain (1A+ Level). However, it is only recommended for patients with significant surgical risk factors and for patients with mild radiographic disease in whom conservative treatment has failed (2B± Level). Botulinum toxin type A injection is effective in reducing arthritic knee pain (2B+ Level), and so is tropisetron (2B+ Level) and tanezumab (2B+ Level). The new agents, such as rAAV2-TNFR:Fc, SB-210396/CE 9.1, and various radioisotopes have provided various degrees of success, but their long-term safety and efficacy remains to be determined.

CONCLUSIONS:

We conclude that strong evidence supports the use of intraarticular knee injection as a valuable intervention in the continuum of management of arthritis between conservative treatment and knee surgeries.

01 Apr 2010·The Journal of rheumatologyQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: Ruderman, Eric M. ; Burch, Francis X. ; Mease, Philip J. ; Hobbs, Kathryn F. ; Willis, Larry ; Maricic, Michael J. ; Forstot, Joseph Z. ; Pritchard, Charles H. ; Fudman, Edward J. ; Dao, Kathryn H. ; Trapp, Robert G. ; Fiske, Darrell N. ; Graham, Galen E. ; Wei, Nathan ; Prupas, H. Malin ; Bookbinder, Stephen A. ; Wiesenhutter, Craig W. ; Greenwald, Maria ; Heald, Alison E. ; Anklesaria, Pervin ; Schechtman, Joy ; Hou, Antony ; Kivitz, Alan J.

Objective.:

To 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.

Methods.:

In 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 × 1011, 1 × 1012, or 1 × 1013DNase-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.

Results.:

127 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).

Conclusion.:

IA 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.

08 Dec 2007·BMJ (Clinical research ed.)

US gene therapy trial is to restart, despite patient’s death

Author: Tanne, Janice Hopkins

The US Food and Drug Administration has allowed the resumption of clinical trials of an experimental form of gene therapy for inflammatory arthritis. Trials were suspended in July when a patient died after a second injection into the knee joint of the gene based therapy developed by Targeted Genetics Corporation of Seattle, Washington. Targeted Genetics said in a press release that the FDA had reviewed data on safety concerning all 127 patients in the trial of the treatment, which used tgAAC94, an investigational gene therapy product developed to treat active inflammatory arthritis, as well as data from the patient who died. The investigation found that the drug did not contribute to her death, the company said. The Recombinant Advisory Committee of the National Institutes …

News (Medical) associated with tgAAC 94

25 May 2006

·www.biospace.com

Targeted Genetics Corporation Highlights Inflammatory Arthritis Program And Robust AAV Product Development Platform At The American Society Of Gene Therapy Annual Meeting

SEATTLE--(BUSINESS WIRE)--May 25, 2006--Targeted Genetics Corporation (Nasdaq:TGEND - News) and its academic and corporate collaborators will report data in 14 presentations at the 9th Annual Meeting of the American Society of Gene Therapy (ASGT). The meeting will take place June 1 - June 5 in Baltimore, Maryland. Two presentations will discuss preliminary safety and efficacy data from an ongoing Phase I/II clinical trial of tgAAC94 in patients with inflammatory arthritis, and two additional presentations will describe other advances in the company's inflammatory disease program. Research conducted by Dr. John Engelhardt, Ph.D., Director of the Center for Gene Therapy, and Professor, Department of Anatomy and Cell Biology, at the University of Iowa, and funded by Targeted Genetics, will be featured as one of the "Top Five Abstracts" at the Presidential Symposium on June 3rd (Abstract # 807). Additional presentations will focus on advances in AAV manufacturing, basic and applied AAV biology and Targeted Genetics' collaborations in the areas of Huntington's disease and congestive heart failure.

Gene TherapyCollaborate

100 Deals associated with tgAAC 94

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Indication	Highest Phase	Country/Location	Organization	Date
Ankylosing Spondylitis	Phase 2	United States	AmpliPhi Biosciences Corp.	01 Aug 2005
Arthritis, Psoriatic	Phase 2	United States	AmpliPhi Biosciences Corp.	01 Aug 2005
Rheumatoid Arthritis	Phase 2	United States	AmpliPhi Biosciences Corp.	01 Aug 2005
Periodontal Diseases	Phase 2	-	Armata Pharmaceuticals, Inc.	-

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