Rheumatoid ArthritisPhase 1NCT00617032
Phase 1 Dose Escalation Study of Intra-Articular Administration of tgAAC94
A Phase 1 study testing tgAAC94 gene therapy vector in people with Rheumatoid Arthritis, run by Targeted Genetics Corporation at 7 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- tgAAC94 gene therapy vector
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Feb 2004to Nov 2005
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis, diagnosed according to published criteria
- Persistent moderate (grade 2) or sever (grade 3) swelling due to inflammatory arthritis in at least one peripheral joint eligible for injection
- For subjects with rheumatoid arthritis, an adequate trial of at least one disease-modifying antirheumatic drug (DMARD) prior to screening
- For subjects currently on DMARD(s), a stable regimen for inflammatory arthritis for the previous three months, with no changes in doses in the four weeks prior to screening
- Age greater than 18 years
- Be willing to practice effective birth control measures during the study, if of reproductive ability
- Able to give written informed consent
Who cannot join
- Current use of a TNF-alpha antagonist
- Disease severe enough to warrant use of a systemic TNF-alpha antagonist in the next three months
- Discontinuation of TNF-alpha antagonists in the past because of safety concerns
- Current use of anakinra
- Poor functional status, defined as being bed-bound or wheelchair-bound
- Corticosteriod therapy at doses higher than the equivalent of 10 mg prednisone per day
Show all 13Show fewer
- Any of the following laboratory values: Hemoglobin <8.5 gm/dL, white blood cell count <3500 per mm^3, platelet <100 K/microL, creatinine >2 mg/dL, bilirubin >2 mg/dL, AST or ALT >2 times the upper limit of normal, or abnormal coagulation profiles
- 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 six months
- Inflammatory bowel disease, such as Crohn's disease or ulcerative colitis
- Serious medical disease, such as sever liver or kidney disease, uncompensated congestive heart failure, myocardial infarction within six months, unstable angina, uncontrolled hypertension, severe pulmonary disease or active 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 the protocol
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Canada4 sites
Mt Sinai Hospital
Toronto, Ontario
Toronto Western Hospital
Toronto, Ontario
Arthritis Research Centre of Canada
Vancouver, British Columbia
Arthritis Centre Clinical Research Unit UofManitoba
Winnipeg, Manitoba
United States3 sites
Denver Arthritis Research Center
Denver, Colorado
UCLA Division of Rheumatology
Los Angeles, California
Swedish Rheumoatology Research
Seattle, Washington
About this study
Official title: 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.
Read the detailed description
tgAAC94 is a recombinant adeno-associated virus serotype 2 (AAV2) vector genetically engineered to contain the cDNA for a human tumor necrosis factor receptor (TNFR)-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) gene. The DNA sequence of TNFR:Fc in tgAAC94 codes for a protein sequence identical to etanercept (Enbrel). TNF-alpha has been strongly implicated as a major participant in the inflammatory cascade that leads to joint damage and destruction in diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS).
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 inflammatory 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 inflammatory arthritis.
- Conditions
- Rheumatoid Arthritis
- Being tested
- tgAAC94 gene therapy vector, tgAAC94 placebo
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tgAAC94 gene therapy vectorGenetic
Single Dose 1x10^10 DNase resistant particles (DRP) / mL joint volume
tgAAC94 gene therapy vectorGenetic
Single dose 1x10^11 DNase resistant particles (DRP) / mL joint volume
tgAAC94 placeboGenetic
Single dose
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | 1x10^10 DRP/mL tgAAC94 Receives: Genetic: tgAAC94 gene therapy vector |
| 2 | Active comparator | 1x10^11 DRP/mL tgAAC94 Receives: Genetic: tgAAC94 gene therapy vector |
| 3 | Placebo comparator | Single dose tgAAC94 placebo Receives: Genetic: tgAAC94 placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serious adverse events
Measured: From study drug administration through final study visit
Severe or very severe adverse events
Measured: From study drug administration through final study visit
Study drug-related adverse events
Measured: From study drug administration through final study visit
Secondary outcomes (7)
Change in tenderness and swelling of injected joint
Measured: Days 3 and 7 and Weeks 2, 4, 8, and 12
Change in tenderness and swelling of non-injected joints
Measured: Weeks 2, 4, and 12
Reduction in disease activity, as measured by American College of Rheumatology (ACR) criteria and Disease Activity Score (DAS)
Measured: Weeks 2, 4, and 12
Joint fluid measures (cell count and differential, total protein and TNFR:Fc protein)
Measured: Weeks 4 and 12
TNFR:Fc protein levels in serum
Measured: Day 7 and Weeks 2, 4, 8, and 12
Serum neutralizing antibodies to AAV2
Measured: Weeks 4 and 12
Presence of tgAAC94 in peripheral blood mononuclear cells (PBMCs)
Measured: Day 3 and Weeks 2 and 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2008 (estimated)
- Study startFeb 2004
- Primary completionNov 2005
- Study completionNov 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Targeted Genetics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Alison Heald, MD, Study director, Targeted Genetics Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00617032
- Sponsor's protocol ID
- 13E04
- Other IDs
- RAC Protocol # 0307-588, HPB 0088676
- Status last verified
- Feb 2008
- First submitted
- 5 Feb 2008
- Last updated
- 15 Feb 2008
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00617032
- Acronym / sponsor ID
- 13E04
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Targeted Genetics CorporationIndustry (pharma, biotech, devices)
- Study start
- Feb 2004
- Primary completion
- Nov 2005 (actual)
- Study completion
- Nov 2005 (actual)
- First posted
- 15 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
tgAAC94 is a recombinant adeno-associated virus serotype 2 (AAV2) vector genetically engineered to contain the cDNA for a human tumor necrosis factor receptor (TNFR)-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) gene. The DNA sequence of TNFR:Fc in tgAAC94 codes for a protein sequence identical to etanercept (Enbrel). TNF-alpha has been strongly implicated as a major participant in the inflammatory cascade that leads to joint damage and destruction in diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS).
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 inflammatory 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 inflammatory arthritis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Genetic: tgAAC94 gene therapy vector1x10^10 DRP/mL tgAAC94 |
| 2 | Active comparator | Genetic: tgAAC94 gene therapy vector1x10^11 DRP/mL tgAAC94 |
| 3 | Placebo comparator | Genetic: tgAAC94 placeboSingle dose tgAAC94 placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis, diagnosed according to published criteria
- Persistent moderate (grade 2) or sever (grade 3) swelling due to inflammatory arthritis in at least one peripheral joint eligible for injection
- For subjects with rheumatoid arthritis, an adequate trial of at least one disease-modifying antirheumatic drug (DMARD) prior to screening
- For subjects currently on DMARD(s), a stable regimen for inflammatory arthritis for the previous three months, with no changes in doses in the four weeks prior to screening
- Age greater than 18 years
Key exclusion criteria (13 listed)
- Current use of a TNF-alpha antagonist
- Disease severe enough to warrant use of a systemic TNF-alpha antagonist in the next three months
- Discontinuation of TNF-alpha antagonists in the past because of safety concerns
- Current use of anakinra
- Poor functional status, defined as being bed-bound or wheelchair-bound
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tgAAC94 gene therapy vectorSingle Dose 1x10^10 DNase resistant particles (DRP) / mL joint volume | Genetic | 1 |
| tgAAC94 gene therapy vectorSingle dose 1x10^11 DNase resistant particles (DRP) / mL joint volume | Genetic | 2 |
| tgAAC94 placeboSingle dose | Genetic | 3 |
Primary outcome
Serious adverse events
Time frame: From study drug administration through final study visit
Severe or very severe adverse events
Time frame: From study drug administration through final study visit
Study drug-related adverse events
Time frame: From study drug administration through final study visit
7 secondary outcomes
Change in tenderness and swelling of injected joint
Time frame: Days 3 and 7 and Weeks 2, 4, 8, and 12
Change in tenderness and swelling of non-injected joints
Time frame: Weeks 2, 4, and 12
Reduction in disease activity, as measured by American College of Rheumatology (ACR) criteria and Disease Activity Score (DAS)
Time frame: Weeks 2, 4, and 12
Joint fluid measures (cell count and differential, total protein and TNFR:Fc protein)
Time frame: Weeks 4 and 12
TNFR:Fc protein levels in serum
Time frame: Day 7 and Weeks 2, 4, 8, and 12
Serum neutralizing antibodies to AAV2
Time frame: Weeks 4 and 12
Presence of tgAAC94 in peripheral blood mononuclear cells (PBMCs)
Time frame: Day 3 and Weeks 2 and 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alison Heald, MD study director
Targeted Genetics Corporation
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing tgAAC94 gene therapy vector in people with Rheumatoid Arthritis, run by Targeted Genetics Corporation at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serious adverse events (time frame: From study drug administration through final study visit). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2008.