Anti-TNF Agents for the Treatment of Rheumatoid Arthritis
This study is currently recruiting participants.
Verified November 2012 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00837434
First received: February 3, 2009
Last updated: November 7, 2012
Last verified: November 2012
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Purpose
Rheumatoid arthritis (RA) is a chronic disease that leads to inflammation and progressive joint damage. RA is a systemic inflammatory autoimmune disorder affecting almost 1% of the United States population. Current therapies target the immune system early in the disease process before joint damage occurs, and include drugs such as methotrexate (MTX) and tumor necrosis factor (TNF)-blocking agents. The primary purpose of this study is to determine the effectiveness of two TNF inhibitors, etanercept and adalimumab, on memory B lymphocytes (B-cells) in the peripheral blood of participants with RA.
Additionally, there are 4 optional sub-studies as part of the trial:
- B-Cell Kinetic Sub-Study to look at changes in B-cell subsets over time and how quickly reductions in B-cell memory occur.
- Vaccine Response Sub-Study to assess B cell memory in response to immunization with hepatitis B,-hepatitis A, and diphtheria/tetanus vaccines, and to determine whether T-cell vaccine responses are altered with TNF blockade.
- Tonsil Biopsy Sub-Study to evaluate how TNF blockade affects memory B-cells in the tonsil dendritic cells and germinal cells.
- Synovial Biopsy Sub-Study to evaluate how TNF blockade affects changes in memory B-cells in lymphoid tissue.
| Condition | Intervention | Phase |
|---|---|---|
|
Rheumatoid Arthritis |
Drug: Etanercept Drug: Adalimumab |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Single Blind (Investigator) Primary Purpose: Treatment |
| Official Title: | A Partially Blinded, Randomized, Multi-Center, Phase IV Trial to Evaluate Mechanism of Action of Anti-TNF Agents in Rheumatoid Arthritis |
Resource links provided by NLM:
Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):
Primary Outcome Measures:
- Change in memory B-cells in peripheral blood [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Frequency of adverse events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Frequency of serious adverse events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Frequency of treatment-related AEs of National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 3 or higher [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Change in DAS28 score [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- ACR20 and ACR50 responses [ Time Frame: At Weeks 12 and 24 ] [ Designated as safety issue: No ]
- DAS28 responder status [ Time Frame: At Weeks 12 and 24 ] [ Designated as safety issue: No ]
- B-cell subset fractions in peripheral blood [ Time Frame: At Weeks 12 and 24 ] [ Designated as safety issue: No ]
- T-cell subset fraction in peripheral blood [ Time Frame: At Weeks 12 and 24 ] [ Designated as safety issue: No ]
- Changes in autoantibody status [ Time Frame: At study entry and Weeks 12 and 24 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 60 |
| Study Start Date: | March 2009 |
| Estimated Study Completion Date: | September 2013 |
| Estimated Primary Completion Date: | September 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Etanercept Injection
Participants will receive a subcutaneous injection of etanercept once every week for 24 weeks
|
Drug: Etanercept
0.98 mL of 50 mg/mL solution of etanercept with 10 mg/mL sucrose, 5.8 mg/mL sodium chloride, 5.3 mg/mL L-arginine hydrochloride, 2.6 mg/mL sodium phosphate monobasic monohydrate, and 0.9 mg/mL sodium phosphate dibasic anhydrous
Other Name: Enbrel
|
|
Experimental: Adalimumab Injection
Participants will receive a subcutaneous injection of adalimumab once every 2 weeks for 24 weeks
|
Drug: Adalimumab
0.8 mL of 40 mg/mL solution of adalimumab with 4.93 mg sodium chloride, 0.69 mg monobasic sodium phosphate dehydrate, 1.22 mg dibasic sodium phosphate dehydrate, 0.24 mg sodium citrate, 1.04 mg citric acid monohydrate, 9.6 mg mannitol, 0.8 mg polysorbate 80, and water
Other Name: Humira
|
Detailed Description:
RA is characterized by persistent inflammation of peripheral joints, causing pain, stiffness, swelling, and warmth. Over the past 10 years, advancements in biotechnology have revolutionized RA therapeutics with biologically-derived immunomodulating compounds. TNF-alpha inhibitors constitute the largest class of these new biologic therapies. The purpose of this study is to determine the effectiveness two TNF inhibitors, etanercept and adalimumab, on memory B lymphocytes (B-cells) in the peripheral blood of participants with RA.
This study will last 24 weeks. Participants will be randomized into one of two arms. Participants in Arm 1 will receive a subcutaneous injection of etanercept once every week for 24 weeks. Participants in Arm 2 will receive a subcutaneous injection of adalimumab once every 2 weeks for 24 weeks.
This study consists of seven study visits after randomization and will occur at study entry and Weeks 4, 8, 12, 16, 20 and 24. Blood collection will occur at all study visits. A written participant assessment, vital signs, and physical exam will occur at study entry and Weeks 12 and 24. Follow-up calls to assess safety are scheduled for Weeks 4, 8, 16, and 20.
Additionally, participants will be offered the opportunity to enter one of four sub-studies as mentioned in the brief summary above: B Cell Kinetic Sub-Study, Vaccine Response Sub-Study, Tonsil Biopsy Sub-Study, and Synovial Biopsy Sub-Study. More information on these sub-studies can be found in the protocol.
Eligibility| Ages Eligible for Study: | 18 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of RA. More information on this criterion can be found in the protocol.
- Disease duration as defined from the onset of symptoms of at least 3 months prior to study entry
- Active RA with DAS28 > 4.4, clinically requiring the addition of anti-TNF therapy
- Stable dose of MTX between 7.5 mg and 25 mg weekly for at least 8 weeks prior to study entry
- Able and willing to self-administer subcutaneous injections or have available qualified person(s) or caregiver to administer subcutaneous injections
- For females, agree to use accepted methods of contraception during the duration of the study and for 150 days after study completion. More information on this criterion can be found in the protocol.
Exclusion Criteria:
- Positive PPD (> 5 mm induration regardless of prior Bacille Calmette Guerin [BCG] vaccine administration) without evidence of ongoing treatment for at least 30 days or completed treatment
- History of positive PPD or chest x-ray findings indicative of prior TB infection, without documentation of either treatment for TB infection or chemoprophylaxis for TB exposure
- Prednisone dose > 10 mg/day (or equivalent dose of another corticosteroid) within 30 days prior to study entry
- Definitive diagnosis of another autoimmune disease that may require immunosuppression for treatment. More information on this criterion can be found in the protocol.
- Concomitant use of DMARDSs. More information on this criterion can be found in the protocol.
- Any immunosuppressive therapy other than MTX, NSAIDs, or corticosteroids. More information on this criterion can be found in the protocol.
- Current or previous use of any biologic agent
- Presence of open leg ulcers
- Chronic or persistent infection that might be worsened by immunosuppressive treatment. More information on this criterion can be found in the protocol.
- Active infection or severe infections requiring hospitalization or treatment with IV antibiotics, IV antivirals, or IV antifungals within 30 days prior to study entry
- Received oral antibiotics, antivirals, or antifungals within 14 days prior to study entry
- Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
- Any medical condition that, in the opinion of the investigator, would interfere with the study
- History of malignancy other than treated localized carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell skin carcinoma within 10 years prior to study entry
- Any Investigational agent within the earlier of 4 weeks or 5 half-lives prior to study entry
- History of drug or alcohol abuse within 6 months prior to study entry
- Known allergy or hypersensitivity to study products
- Inability or unwillingness to follow the protocol
- Any condition or treatment that, in the opinion of the investigator, places the participant at an unacceptable risk
- Pregnant or breastfeeding
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00837434
Locations
| United States, Alabama | |
| University of Alabama | Recruiting |
| Birmingham, Alabama, United States | |
| Contact: Laticia Woodruff 205-934-9843 laticia.woodruff@ccc.uab.edu | |
| Principal Investigator: Jeffrey Curtis, MD | |
| United States, California | |
| University of California, San Francisco | Recruiting |
| San Francisco, California, United States | |
| Contact: Steve Lund 415-502-5278 stevel@medicine.ucsf.edu | |
| Principal Investigator: Jonathan Graf, MD | |
| United States, Connecticut | |
| Yale University School Medicine | Recruiting |
| New Haven, Connecticut, United States, 06519 | |
| Contact: Viviane Bunin, MD 203-737-5430 | |
| Principal Investigator: Insoo Kang, MD | |
| United States, Illinois | |
| University of Chicago | Recruiting |
| Chicago, Illinois, United States | |
| Contact: Jori Reigle 773-834-5357 jreigle@medicine.bsd.uchicago.edu | |
| Principal Investigator: Richard Keating, MD | |
| United States, New York | |
| Feinstein Institute for Medical Research | Recruiting |
| Manhassett, New York, United States, 11030 | |
| Contact: Andrew Shaw 516-562-2591 anshaw@nshs.edu | |
| Principal Investigator: Meggan Mackay, MD | |
| University of Rochester | Recruiting |
| Rochester, New York, United States | |
| Contact: Kelly Callahan 585-275-1635 kelly_callahan@urmc.rochester.edu | |
| Principal Investigator: Jennifer Anolik, MD | |
| United States, South Carolina | |
| Medical University of South Carolina | Recruiting |
| Charleston, South Carolina, United States, 29425 | |
| Contact: Dana Rosson 843-792-2014 rosson@musc.edu | |
| Principal Investigator: Marcy Bolster, MD | |
Sponsors and Collaborators
Investigators
| Study Chair: | Jennifer A. Anolik, MD, PhD | University of Rochester |
| Study Chair: | Inaki Sanz, MD | University of Rochester |
| Study Chair: | R. John Looney, MD | University of Rochester |
| Principal Investigator: | Meggan Mackay, MD | The Feinstein Institute for Medical Research NS-LIJ Health System |
| Principal Investigator: | Jeffrey Curtis, MD | University of Alabama at Birmingham |
More Information
Publications:
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00837434 History of Changes |
| Other Study ID Numbers: | DAIT ARA06 |
| Study First Received: | February 3, 2009 |
| Last Updated: | November 7, 2012 |
| Health Authority: | United States: Federal Government |
Additional relevant MeSH terms:
|
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases TNFR-Fc fusion protein Adalimumab Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic |
Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Pharmacologic Actions Anti-Inflammatory Agents Therapeutic Uses Antirheumatic Agents Gastrointestinal Agents Immunologic Factors Immunosuppressive Agents Central Nervous System Agents |
ClinicalTrials.gov processed this record on May 19, 2013