Study of Intra-articular Delivery of tgAAC94 in Inflammatory Arthritis Subjects
NCT ID: NCT00126724
Last Updated: 2009-07-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1/PHASE2
120 participants
INTERVENTIONAL
2005-08-31
2009-05-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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).
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
BG9924 in Combination With Methotrexate for Participants With Active Rheumatoid Arthritis
NCT00458861
Repository Corticotropin Injection To Treat Rheumatoid Arthritis Patients Who Have Failed Three Biologic Therapies.
NCT01966718
A Study of RoActemra/Actemra (Tocilizumab) Given Subcutaneously in Combination With Traditional DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis
NCT01232569
A Study to Assess the Effect of Tocilizumab + Methotrexate on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis
NCT00106548
A Study of LY4213663 in Healthy Participants and Participants With Rheumatoid Arthritis
NCT07258849
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Intra-articular delivery of the TNFR:Fc gene (tgAAC94) should result in expression of the secreted protein in the joint space and provide local high concentrations of soluble TNFR:Fc for an extended period of time without requiring frequent administration. Thus, this proposed therapy would be useful in those inflammatory arthritis patients who have a persistently problematic joint despite the use of systemic TNF-alpha blockade or who have a limited number of arthritic joints.
Extensive preclinical studies using rAAV2 containing several different transgenes in a variety of animal models have shown efficient and persistent gene transfer and expression with minimal toxicity. The parent virus (wild-type AAV2) is a naturally occurring, non-replicating virus that depends on a helper virus, such as adenovirus, for replication. The recombinant AAV2 vector is unable to replicate in target host cells because it lacks the AAV genes, whose protein products are also required in trans, for replication and packaging of progeny virus. Extensive epidemiological studies have found AAV2 to be non-pathogenic.
Although there is no cure for arthritis, treatment has been revolutionized by the advent of anti-TNF-alpha therapies. These include etanercept (Enbrel®), infliximab (Remicade®) and adalimumab (Humira®), which consist of soluble TNF receptors, chimeric human-mouse anti-TNF-alpha monoclonal antibodies and fully human anti-TNF-alpha monoclonal antibodies, respectively. Clinical studies have shown these products to improve the signs and symptoms, inhibit the structural damage, and impact functional outcomes in patients with these inflammatory arthritides.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
1
1x10\^11 DRP/mL tgAAC94
tgAAC94 gene therapy vector
Single Dose 1x10\^11 DRP/mL
tgAAC94 gene therapy vector
Second dose of 1x10\^11 DRP/mL tgAAC94 administered once target joint reaches predetermined criteria for re-injection (on or after Week 12) at the same concentration as initial dose.
2
1x10\^12 DRP/mL tgAAC94
tgAAC94 gene therapy vector
Single Dose 1x10\^12 DRP/mL tgAAC94
tgAAC94 gene therapy vector
Second dose of 1x10\^12 DRP/mL tgAAC94 administered once target joint reaches predetermined criteria for re-injection (on or after Week 12) at the same concentration as initial dose.
3
1x10\^13 DRP/mL tgAAC94
tgAAC94 gene therapy vector
Single Dose 1x10\^13 DRP/mL tgAAC94
tgAAC94 gene therapy vector
Second dose of 1x10\^13 DRP/mL tgAAC94 administered once target joint reaches predetermined criteria for re-injection (on or after Week 12) at the same concentration as initial dose.
4
tgAAC94 placebo
placebo
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
tgAAC94 gene therapy vector
Single Dose 1x10\^11 DRP/mL
tgAAC94 gene therapy vector
Second dose of 1x10\^11 DRP/mL tgAAC94 administered once target joint reaches predetermined criteria for re-injection (on or after Week 12) at the same concentration as initial dose.
tgAAC94 placebo
placebo
tgAAC94 gene therapy vector
Single Dose 1x10\^12 DRP/mL tgAAC94
tgAAC94 gene therapy vector
Second dose of 1x10\^12 DRP/mL tgAAC94 administered once target joint reaches predetermined criteria for re-injection (on or after Week 12) at the same concentration as initial dose.
tgAAC94 gene therapy vector
Single Dose 1x10\^13 DRP/mL tgAAC94
tgAAC94 gene therapy vector
Second dose of 1x10\^13 DRP/mL tgAAC94 administered once target joint reaches predetermined criteria for re-injection (on or after Week 12) at the same concentration as initial dose.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Persistent moderate (grade 2) or severe (grade 3) swelling due to inflammatory arthritis in at least one peripheral joint eligible for injection.
* For subjects with RA, an adequate trial of at least one disease-modifying drug (DMARD) prior to screening.
* For subjects currently on DMARD(s), a stable regimen of inflammatory arthritis for the previous three months, with no changes in doses four weeks prior to screening.
* Age greater than 18 years and less than 75 years at the time of screening.
* Willingness to practice effective birth control measures during the study (through week 36), if male or female of reproductive ability.
* Able to give written informed consent.
Exclusion Criteria
* Discontinuation of etanercept in the past because of safety concerns.
* Current use of anakinra (Kineret®)or abatacept (Orencia®).
* Corticosteroid therapy at doses higher than the equivalent of 10 mg prednisone per day.
* Steroid or hyaluronate injection in the target joint or receipt of an investigational agent less than four weeks prior to screening.
* Class IV ACR functional status (Hochberg et al., 1992).
* Any of the following laboratory values: Hemoglobin \<8.5 gm/dL, white blood cell count \<3500 per mm cube, platelet \<100 K/uL, creatinine \>2 mg/dL, bilirubin \>2 mg/dL, AST or ALT \>2 times the upper limit of normal, or abnormal coagulation profiles (\>2 seconds beyond upper range of normal PT or PTT).
* Known HIV infection, known hepatitis C infection, or known positive serologic test for hepatitis B surface antigen.
* Positive PPD, unless previously treated with appropriate prophylaxis.
* Pregnancy or lactation, either at the time of screening or planned in the next 18 months.
* Inflammatory bowel disease, such as Crohn's disease or ulcerative colitis.
* Serious medical disease, such as severe liver or kidney disease, uncompensated congestive heart failure, myocardial infarction within six months, unstable angina, uncontrolled hypertension, severe pulmonary disease or uncontrolled asthma, demyelinating neurological disease, history of cancer (other than cutaneous basal and squamous cell carcinoma) with less than five years documentation of a disease-free state, insulin-dependent diabetes, recurrent opportunistic infections or other concurrent medical condition that, in the opinion of the investigator, would make the subject unsuitable for the study.
* Unlikely to comply with protocol.
18 Years
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Targeted Genetics Corporation
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Targeted Genetics Corporation
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Alison Heald, MD
Role: STUDY_DIRECTOR
Targeted Genetics Corporation
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Sun Valley Arthritis Center
Glendale, Arizona, United States
Catalina Pointe Clinical Research, Inc
Tuscon, Arizona, United States
Desert Medical Advances
Palm Desert, California, United States
Boling Clinical Trials
Upland, California, United States
Denver Arthritis Research Center
Denver, Colorado, United States
RASF-Clinical Research Center
Boca Raton, Florida, United States
Ocala Rheumatology Research Center
Ocala, Florida, United States
Radiant Research Stuart
Stuart, Florida, United States
Coeur d'Alene Arthritis Clinic
Coeur d'Alene, Idaho, United States
Northwestern Center for Clinical Research
Chicago, Illinois, United States
The Arthritis Center
Springfield, Illinois, United States
Arthritis and Osteoporosis Center of Maryland
Frederick, Maryland, United States
Arthritis Center of Reno
Reno, Nevada, United States
United Medical Associates
Johnson City, New York, United States
Bone and Joint Hospital Research Dept.
Oklahoma City, Oklahoma, United States
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States
Rheumatic Disease Associates
Willow Grove, Pennsylvania, United States
Austin Rheumatology Research
Austin, Texas, United States
Arthritis Consultation Center
Dallas, Texas, United States
Metroplex Clinical Research Center
Dallas, Texas, United States
Radiant Research San Antonio Northeast
San Antonio, Texas, United States
Seattle Rheumatology Associates, PLLC
Seattle, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Heald AE, Fudman EJ, Anklesaria P, Mease PJ; 13G01 Study Team. Single-joint outcome measures: preliminary validation of patient-reported outcomes and physical examination. J Rheumatol. 2010 May;37(5):1042-8. doi: 10.3899/jrheum.090827. Epub 2010 Mar 15.
Frank KM, Hogarth DK, Miller JL, Mandal S, Mease PJ, Samulski RJ, Weisgerber GA, Hart J. Investigation of the cause of death in a gene-therapy trial. N Engl J Med. 2009 Jul 9;361(2):161-9. doi: 10.1056/NEJMoa0801066.
Related Links
Access external resources that provide additional context or updates about the study.
Sponsor Home Page
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NIH Protocol Number: 0504-705
Identifier Type: -
Identifier Source: secondary_id
13G01
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.