Study of Intra-articular Delivery of tgAAC94 in Inflammatory Arthritis Subjects
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
2 other identifiers
interventional
120
1 country
22
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2005
Typical duration for phase_1
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2005
CompletedFirst Submitted
Initial submission to the registry
August 2, 2005
CompletedFirst Posted
Study publicly available on registry
August 4, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2009
CompletedJuly 29, 2009
July 1, 2009
3.2 years
August 2, 2005
July 27, 2009
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Serious adverse events
From time of study drug administration through final study visit
Severe or very severe adverse events
From time of study drug administration through final study visit
Study-drug related adverse events
From time of study drug administration through final study visit
Secondary Outcomes (6)
Change in tenderness and swelling of target joint
All scheduled study visits
Time to qualifying for second injection of study drug
Week A12 or 18 or 24
Reduction in disease activity, as measured by American College of Rheumatology (ACR) criteria, Disease Activity Score (DAS) or Assessments in Ankylosing Spondylitis (ASAS) criteria, as applicable
Day A0, Weeks A4, 8, 12, 18, 24, Day B0, Weeks B4, B8, B12, B18, B24, B30, withdrawal
Human tumor necrosis factor receptor (TNFR)-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) protein levels in synovial fluid and serum
Serum: Days A0,7,Weeks A4,12,24, Days B0,7,Weeks 8,12,18,24,30, withdrawal. Synovium: Days A0,4,Weeks A12,24, Day B0,Weeks 4,12,24, withdrawal
Serum anti-adeno-associated virus serotype 2 (AAV2) capsid neutralizing antibodies
Day A0, Weeks A4, 12, 24, Day B0, Weeks B4, 12,24, 30, withdrawal
- +1 more secondary outcomes
Study Arms (4)
1
ACTIVE COMPARATOR1x10\^11 DRP/mL tgAAC94
2
ACTIVE COMPARATOR1x10\^12 DRP/mL tgAAC94
3
ACTIVE COMPARATOR1x10\^13 DRP/mL tgAAC94
4
PLACEBO COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- Rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) diagnosed according to established 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.
You may not qualify if:
- Disease severe enough to warrant a change in regimen for inflammatory arthritis in the next three months.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
Sun Valley Arthritis Center
Glendale, Arizona, 85308, United States
Catalina Pointe Clinical Research, Inc
Tuscon, Arizona, 85704, United States
Desert Medical Advances
Palm Desert, California, 92260, United States
Boling Clinical Trials
Upland, California, 91786, United States
Denver Arthritis Research Center
Denver, Colorado, 80230, United States
RASF-Clinical Research Center
Boca Raton, Florida, 33486, United States
Ocala Rheumatology Research Center
Ocala, Florida, 34474, United States
Radiant Research Stuart
Stuart, Florida, 34996, United States
Coeur d'Alene Arthritis Clinic
Coeur d'Alene, Idaho, 83814, United States
Northwestern Center for Clinical Research
Chicago, Illinois, 60611, United States
The Arthritis Center
Springfield, Illinois, 62704, United States
Arthritis and Osteoporosis Center of Maryland
Frederick, Maryland, 21702, United States
Arthritis Center of Reno
Reno, Nevada, 89502, United States
United Medical Associates
Johnson City, New York, 13790, United States
Bone and Joint Hospital Research Dept.
Oklahoma City, Oklahoma, 73103, United States
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635, United States
Rheumatic Disease Associates
Willow Grove, Pennsylvania, 19090, United States
Austin Rheumatology Research
Austin, Texas, 78705, United States
Arthritis Consultation Center
Dallas, Texas, 75231, United States
Metroplex Clinical Research Center
Dallas, Texas, 75235, United States
Radiant Research San Antonio Northeast
San Antonio, Texas, 78217, United States
Seattle Rheumatology Associates, PLLC
Seattle, Washington, 98104, United States
Related Publications (2)
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.
PMID: 20231202DERIVEDFrank 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.
PMID: 19587341DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Alison Heald, MD
Targeted Genetics Corporation
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
Study Record Dates
First Submitted
August 2, 2005
First Posted
August 4, 2005
Study Start
August 1, 2005
Primary Completion
October 1, 2008
Study Completion
May 1, 2009
Last Updated
July 29, 2009
Record last verified: 2009-07