Enbrel-Sulfasalazin-Early-Axial Spondyloarthritis (AS)

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ClinicalTrials.gov Identifier: NCT00844142

Recruitment Status : Unknown

Verified February 2009 by Charite University, Berlin, Germany.
Recruitment status was: Recruiting

First Posted : February 13, 2009

Last Update Posted : February 13, 2009

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Wyeth is now a wholly owned subsidiary of Pfizer

Information provided by:

Charite University, Berlin, Germany

Study Description

Brief Summary:

Efficacy - To assess efficacy of etanercept versus sulfasalazine when added to NSAIDs in patients with moderate to severe active early axial spondyloarthritis duration of ongoing axial symptoms of less than 5 years. Primary outcome is change of active inflammatory lesions in sacroiliac joints and spine as detected by MRI at 12 months. Secondary outcome parameters are clinical and laboratory efficacy parameters and MRI changes at 6 months and 2 years. Comparisons will be made within the two treatment arms and compared to baseline. At the 1 year extension phase comparisons will be also made between year 1 and year 2. At the end of the extended study a pelvic x-ray is planned.

Condition or disease	Intervention/treatment	Phase
Moderate to Severe Active Axial Spondyloarthritis	Drug: Etanercept 25mg Drug: Sulfasalazine	Phase 2

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Detailed Description:

Randomized controlled study with two treatment arms (Phase II), 1 year open extension

Efficacy - To assess efficacy of etanercept vs. sulfasalazine when added to NSAIDs in patients with moderate to severe active early axial spondyloarthritis duration of ongoing axial symptoms of less than 5 years. Primary outcome is change of active inflammatory lesions in sacroiliac joints and spine as detected by MRI at 12 months. Secondary outcome parameters are clinical and laboratory efficacy parameters and MRI changes at 6 months and 2 years. Comparisons will be made within the two treatment arms and compared to baseline. At the 1 year extension phase comparisons will be also made between year 1 and year 2. At the end of the extended study a pelvic x-ray is planned. For etanercept group: To assess whether etanercept will show sustained long term response over 1 more year. To assess whether etanercept will slow or stop progression as shown by MRI.For sulfasalazine group: to assess whether etanercept will show long term response over 1 year. To assess whether etanercept will slow or stop progression as shown by MRI. For all patients who are in remission the duration of remission will be assessed for a maximum of one year. In case of a flare of the disease these patients will be (re-) treated with etanercept and efficacy will be assessed. Safety - To study the long-term safety of etanercept in patients with moderate to severe active early axial spondyloarthritis compared to patients treated with sulfasalazine over a period of one year.

Patients will be treated for 1 year either with etanercept 2x25mg per week subcutaneously or with sulfasalazine 2g/ day given orally. Following screening and baseline evaluations, patients will be assessed at week 2, 4, 6, 8, 10, 12, 24, 36 and 48. Efficacy and safety measurements will be recorded throughout the entire study. The study will be followed by a 60 weeks follow-up phase after week 48 (end of treatment phase). In case of flare they will be (re-)treated with etanercept for further 60 weeks (until week 108). All patients from the former etanercept group who are not in remission will continue to be treated with etanercept for 60 weeks (weeks 60, 72, 84, 96, 108). All patients from the former sulfasalazine group who are not in remission will be switched to etanercept for 60 weeks (at weeks 50, 54, 60, 72, 84, 96, 108).

Treatment arms:Arm 1: 40 patients receive etanercept 2x25 mg weekly subcutaneous injectionArm 2: 40 patients receive sulfasalazine up to 2 g/day (up to 3 g/ per day)

Duration of the study:12 months. For patients in remission a 12 months follow up period will be enclosed. Treatment will be continued for patients in case of flare or in patients who did not achieve remission for 60 weeks. The study is planned start at September 2005. Patients will be recruited over a 12 months period. Altogether the duration of the study is up to 51 months. All patients who are willing to participate in the extension will be treated for another 60 weeks.

Patient Population:Only active axial SpA patients with a disease duration (measured from time of ongoing spinal symptoms) of less than 5 years will be included. This implies that patients with both radiological evidence of sacroiliitis (fulfilling the modified New York criteria for AS) and without radiological evidence of sacroiliitis (see inclusion criteria) will be included.

Efficacy Variables:Primary endpoint:· Reduction of active inflammatory lesions in MRI at 12 monthsSecondary endpoints:

ASAS 20%, 40%, 70% response, ASAS criteria for partial remission· BASDAI 20%, 50%, 70% improvement · BASFI · Mobility examinations: BASMI, Chest Wall Expansion· disease controlling antirheumatic therapy criteria (DC-ART20) (5 out of 6)*· CRP, ESR· Quality of Life: SF-36· Numeric Rating Scale (NRS) - physicians global, patients global, general pain, nocturnal pain · Enthesitis index (Maastricht scale)· swollen joint count· EQ-5D· Socio-economic questionnaire· Chronic changes in MRI at 6, 12 months and 108 weeks· Reduction of active inflammatory lesions in MRI at 6 months and chronic lesions at 6 and 12 months and 108 weeks

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	80 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Randomized Controlled 12 Months Trial With Etanercept (Enbrel ®) vs. Sulfasalazine in Early Axial Spondyloarthritis With Focus on Improvement of Acute Inflammatory Lesions as Detected by MRI. Amendment 4: 1-Year Extension of Study
Study Start Date :	November 2005
Estimated Primary Completion Date :	July 2013
Estimated Study Completion Date :	July 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Sulfasalazine Etanercept

Genetic and Rare Diseases Information Center resources: Acute Graft Versus Host Disease Spondylarthropathy

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
1 etanercept 25mg twice weekly	Drug: Etanercept 25mg patients will receive etanercept 25mg twice weekly
Active Comparator: 2 Sulfasalazine 2000- 3000mg daily	Drug: Sulfasalazine in this arm patients will receive sulfasalazine 2000- 3000mg per os daily

Outcome Measures

Primary Outcome Measures :

Primary outcome: Reduction of active inflammatory lesions in MRI at 12 months. [ Time Frame: 108 weeks ]

Secondary Outcome Measures :

Secondary outcome: ASAS 20%, 40%, 70% response, ASAS criteria for partial remission· BASDAI 20%, 50%, 70% improvement · BASFI · [ Time Frame: 108 weeks ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients 18 - 50 years of age who have moderate to severe active axial spondyloarthritis.
Diagnosis made by :Chronic low back pain (duration > 3 months, onset < 45 years of age)plus 3 out of the 6 following criteria if imaging is positive or 4 out of the following 6 criteria if imaging is negative ·
Inflammatory back pain:
- Good or very good response to NSAIDs
- One or more of the following extraspinal manifestations: uveitis, peripheral arthritis, enthesitis, HLA-B27 positive
- Positive imaging: MRI showing acute inflammatory lesions in spine or SIJ (in the past) or bilateral sacroiliitis grade 2-4 or unilateral sacroiliitis grade 3-4 in x-ray not older than 12 months
- Positive family history for SpA
- MRI at screening showing acute inflammatory lesions in SIJ or spine
Active disease is defined as:
- a BASDAI score of >=4
- back pain score (BASDAI question 2) of >= 4 despite concurrent NSAID therapy, or intolerance to NSAIDs.
Other inclusion criteria include, if on prednisone:
- <7.5 mg per day
- stable for 4 weeks prior to baseline
Women of child bearing potential must have a negative pregnancy test at study baseline and use an adequate, effective method of contraception for a duration of 6 months after stop of etanercept therapy. Sexual active men must use an accepted method of contraception for a duration of 6 months after stop of etanercept therapy.
Reading a normal chest/lung x-ray which should have been performed within the last 12 weeks before inclusion
Able to self-administer injectable drug supplies or have a caregiver who will do so.
Able to store injectable test article at 2° to 8° C.

Exclusion Criteria:

Disease duration of longer than 5 years
History of active tuberculosis (TB), histoplasmosis or listeriosis.
History of positive HIV status, known hepatitis B or C
History of malignancy other than carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell skin carcinoma.
Antibiotic treatment within 3 weeks prior to screening.
Previous treatment with TNF-alpha blockers
Treatment with sulasalazine in the last 6 months before participation in the clinical trial
severe internal medical diseases such as severe cardiac, hepatic, gastrointestinal, neurological, psychiatric diseases

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00844142

Contacts

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Contact: Joachim Sieper, MD	0049-30-8445 ext 4535	joachim.sieper@charite.de
Contact: In-Ho Song, MD	0049-30-8445 ext 4795	in-ho.song@charite.de

Locations

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Germany
Charité Campus Mitte, Rheumatology	Recruiting
Berlin, Germany, 10117
Contact: Gerd-Ruediger Burmester, MD 0049-30-450513 ext 025 gerd.burmester@charite.de
Praxis Mielke	Recruiting
Berlin, Germany, 12627
Contact: Mielke, MD 0049-30-994 ext 21 22
Praxis Zinke	Recruiting
Berlin, Germany, 13055
Contact: Silke Zinke, MD 0049-30-98695 ext 231 dr.silke.zinke@t-online.de
Klinikum Buch	Recruiting
Berlin, Germany, 13125
Contact: Andreas Krause, MD 0049-30-94792 ext 380 a.krause@immanuel.de
Waldkrankenhaus	Recruiting
Berlin, Germany, 13589
Contact: Ulrich Prothmann, MD 0049-30-3702- ext 1302 u.prothmann@waldkrankenhaus.com
Schlossparkklinik, Rheumatology	Recruiting
Berlin, Germany, 14059
Contact: Rieke Alten, MD 0049-303264- ext 1333 rieke.alten@schlosspark-klinik.de
Immanuel Krankenhaus	Recruiting
Berlin, Germany, 14109
Contact: Andreas Krause, MD 0049-30-80505- ext 293 a.krause@immanuel.de
Praxis Klopsch	Recruiting
Neubrandenburg, Germany, 17033
Contact: Thilo Klopsch, MD 0049-395- 775 ext 43 24 dr.thilo.klopsch@t-online.de
Praxis Bohl-Bühler	Recruiting
Potsdam, Germany, 14469
Contact: Martin Bohl-Bühler, MD 0049-331- 647352 ext 1 info@Rheumahaus.de

Sponsors and Collaborators

Charite University, Berlin, Germany

Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

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Principal Investigator:	Joachim Sieper, MD	Charite, Campus Benjamin-Franklin, Rheumatology, Berlin, Germany

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Song IH, Hermann KG, Haibel H, Althoff CE, Poddubnyy D, Listing J, Weiss A, Lange E, Freundlich B, Rudwaleit M, Sieper J. Prevention of new osteitis on magnetic resonance imaging in patients with early axial spondyloarthritis during 3 years of continuous treatment with etanercept: data of the ESTHER trial. Rheumatology (Oxford). 2015 Feb;54(2):257-61. doi: 10.1093/rheumatology/keu263. Epub 2014 Aug 19.

Song IH, Hermann KG, Haibel H, Althoff CE, Poddubnyy D, Listing J, Weiss A, Buss B, Freundlich B, Lange E, Alten R, Rudwaleit M, Sieper J. Consistently Good clinical response in patients with early axial spondyloarthritis after 3 years of continuous treatment with etanercept: longterm data of the ESTHER trial. J Rheumatol. 2014 Oct;41(10):2034-40. doi: 10.3899/jrheum.140056. Epub 2014 Jul 15.

Weiss A, Song IH, Haibel H, Listing J, Sieper J. Good correlation between changes in objective and subjective signs of inflammation in patients with short- but not long duration of axial spondyloarthritis treated with tumor necrosis factor-blockers. Arthritis Res Ther. 2014 Jan 30;16(1):R35. doi: 10.1186/ar4464.

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Responsible Party:	Prof. Dr. med. Joachim Sieper, Charité Rheumatology Campus Benjamin-Franklin
ClinicalTrials.gov Identifier:	NCT00844142
Other Study ID Numbers:	M01 Enbrel-Sulfa-Early-AS
First Posted:	February 13, 2009 Key Record Dates
Last Update Posted:	February 13, 2009
Last Verified:	February 2009

Keywords provided by Charite University, Berlin, Germany:


ankylosing spondylitis axial spondyloarthritis magnetic resonance imaging etanercept sulfasalazine

Additional relevant MeSH terms:

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Spondylitis Spondylarthritis Axial Spondyloarthritis Bone Diseases, Infectious Infections Bone Diseases Musculoskeletal Diseases Spinal Diseases Arthritis Joint Diseases Spondylarthropathies Ankylosis Sulfasalazine	Etanercept Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Gastrointestinal Agents Immunosuppressive Agents Immunologic Factors Anti-Infective Agents

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