Clinical trial NCT00478660: An Open-Label Study to Evaluate the Response to Adalimumab in Patients With Active Ankylosing Spondylitis Who Have Failed Standard Therapy or TNF-Alpha Inhibitors (RHAPSODY)
Official title: Review of Safety and Efficacy With Adalimumab in Patients With Active Ankylosing Spondylitis - An Open-Label Study to Evaluate the Response to Adalimumab in Patients Who Have Failed Standard Therapy or TNF-Alpha Inhibitors (RHAPSODY)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ankylosing Spondylitis
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2007-05-25
Enrollment: 1250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Due to the rigor of the clinical development program of adalimumab for the indication of AS, the population of subjects with active AS that could enroll in previous phase 3 studies was limited. Therefore, it is necessary to further evaluate the use of adalimumab in a setting that mimics day-to-day clinical practice to obtain further safety and efficacy data by allowing subjects meeting the characteristics noted below to enter this study:

* Subjects who failed another TNF inhibitor (etanercept, infliximab)
* Subjects with advanced spinal ankylosis
* Subjects with AS associated disorders (i.e., uveitis, IBD, and psoriasis)


Eligibility criteria: Inclusion Criteria:

* Able and willing to give written informed consent and to comply with the requirements of the study protocol
* Males and females 18 years of age or older
* Diagnosis of AS according to the modified New York Criteria for Ankylosing Spondylitis 1984.24
* Documented active AS based on the opinion of a physician for at least 3 months
* Active AS with BASDAI \>= 4 at the Screening Visit
* Unsatisfactory response to standard AS therapies in accordance with the current national guidelines for treatment of AS with TNF inhibitors (if applicable) including a minimum of failing at least one NSAID. National guidelines (if applicable) must be followed if the guidelines are more strict regarding the use of TNF inhibitors for the treatment of AS
* Use of reliable method of contraception, e.g., IUDs, condoms, or hormone (oral, implantable, or injectable) contraceptives by all female subjects of childbearing potential. Subject must follow the manufacture's recommendations of contraception prior to the administration of study drug and through 150 days following the last administration of adalimumab
* Able and willing to self-administer sc injections or have available a suitable person to administer sc injections
* A negative pregnancy test (serum HCG) for women of childbearing potential prior to start of study treatment
* Subject must be evaluated for active and latent TB infection by using a PPD skin test, T SPOT-TB test, chest x-ray and a detailed review of the subject's medical history. Guidelines regarding the treatment of latent TB must be followed prior to the administration of adalimumab

Exclusion Criteria:

* Prior treatment with any investigational agent within 30 days, or five half-lives of the product, which ever is longer
* Treatment within the last six weeks with infliximab or within the last three weeks with etanercept or previous treatment at any time with adalimumab
* Known allergy to excipients of adalimumab formulation
* History of or current acute inflammatory joint disease of origin other than AS, e.g., rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus etc
* Treatment with corticosteroids (prednisolone equivalents) under the following conditions:

  * Dose is \>10 mg/d systemically within the 28 days before screening
  * Intraarticular injections or infiltrations of peripheral joints and tendons within 28 days before or at screening
  * Intraarticular injections of sacroiliac joints without therapeutic response \<=14 days before screening
* Other medical conditions: uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (NYHA III-IV), recent stroke (within three months), chronic leg ulcer and any other condition (e.g., indwelling urinary catheter) which, in the opinion of the investigator, would put the subject at risk by participation in the study
* History of cancer or malignant lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix
* History of positive serology for hepatitis B indicating active infection or history of positive serology for hepatitis C
* History of positive HIV status
* Persistent or recurrent infections or severe infections requiring hospitalization or treatment with iv antibiotics within 30 days, or oral antibiotics within 14 days prior to enrollment
* Previous diagnosis or signs highly indicative of central nervous system demyelinating diseases (e.g., optic neuritis, ataxia, apraxia)
* History of active tuberculosis, histoplasmosis or listeriosis
* Female subjects who are pregnant or breast-feeding
* History of clinically significant drug or alcohol abuse in the last year

Primary outcomes:
measure: ASAS 20/40/50/70
measure: ASAS 5/6
measure: BASDAI score
Secondary outcomes:
measure: Adverse events
measure: Laboratory data
measure: Vital signs
Other outcomes:
Locations:
city: Graz
country: Austria
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Wien
country: Austria
city: Wien
country: Austria
city: Aalst
country: Belgium
city: Belsele
country: Belgium
city: Brugge
country: Belgium
city: Charleroi
country: Belgium
city: Erembodegem
country: Belgium
city: Genk
country: Belgium
city: Gent
country: Belgium
city: Hasselt
country: Belgium
city: Oostende
country: Belgium
city: Frederiksberg
country: Denmark
city: Holstebro
country: Denmark
city: Kolding
country: Denmark
city: Randers
country: Denmark
city: Silkeborg
country: Denmark
city: Helsinki
country: Finland
city: Hyvinkaa
country: Finland
city: Kouvola
country: Finland
city: Turku
country: Finland
city: Aix En Provence
country: France
city: Aix Les Bains
country: France
city: Amiens Cedex
country: France
city: Angers Cedex 1
country: France
city: Belfort
country: France
city: Berck Cedex
country: France
city: Besancon
country: France
city: Bordeaux Cedex
country: France
city: Boulogne Billancourt
country: France
city: Brest Cedex
country: France
city: Caen-Cedex
country: France
city: Cahors
country: France
city: Clermont-ferrand
country: France
city: Corbeil Essonnes
country: France
city: Creteil
country: France
city: Dijon Cedex
country: France
city: Grenoble
country: France
city: Le Kremlin Bicetre
country: France
city: Le Mans
country: France
city: Levin Cedex
country: France
city: Libourne
country: France
city: Lille Cedex
country: France
city: Limoges
country: France
city: Lomme
country: France
city: Lyon Cedex 03
country: France
city: Lyon Cedex 07
country: France
city: Lyon
country: France
city: Marseille Cedex 5
country: France
city: Marseille Cedex
country: France
city: Montivilliers
country: France
city: Montpellier Cedex 5
country: France
city: Mulhouse Cedex
country: France
city: NANTES Cedex
country: France
city: Nice
country: France
city: Orleans Cedex 01
country: France
city: Paris Cedex 10
country: France
city: Paris Cedex 13
country: France
city: Paris
country: France
city: Paris
country: France
city: Pau Cedex
country: France
city: Poitiers
country: France
city: Reims
country: France
city: Rennes Cedex
country: France
city: Saint Brieuc Cedex 1
country: France
city: Saint Etienne
country: France
city: Strasbourg
country: France
city: Toulouse Cedex 9
country: France
city: Tours Cedex
country: France
city: Valenciennes
country: France
city: Vandoeuvre les Nancy
country: France
city: Bad Bentheim
country: Germany
city: Bad Bramstedt
country: Germany
city: Bad Nauheim
country: Germany
city: Bad
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Chemnitz
country: Germany
city: Cottbus
country: Germany
city: Damp
country: Germany
city: Dresden
country: Germany
city: Dresden
country: Germany
city: Duisburg
country: Germany
city: Düsseldorf
country: Germany
city: Erfurt
country: Germany
city: Erlangen
country: Germany
city: Frankfurt
country: Germany
city: Freiburg
country: Germany
city: Goslar
country: Germany
city: Göttingen
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Herne
country: Germany
city: Hildesheim
country: Germany
city: Hofheim
country: Germany
city: Hoyerswerda
country: Germany
city: Jena
country: Germany
city: Kiel
country: Germany
city: Köln
country: Germany
city: Leipzig
country: Germany
city: München
country: Germany
city: München
country: Germany
city: Neubrandenburg
country: Germany
city: Osnabrück
country: Germany
city: Planegg
country: Germany
city: Ratingen
country: Germany
city: Regensburg
country: Germany
city: Rostock
country: Germany
city: Sendenhorst
country: Germany
city: Stuttgart
country: Germany
city: Stuttgart
country: Germany
city: Tübingen
country: Germany
city: Villingen
country: Germany
city: Vogelsang/Gommern
country: Germany
city: Würzburg
country: Germany
city: Zerbst
country: Germany
city: Zeven
country: Germany
city: Athens
country: Greece
city: Athens
country: Greece
city: Athens
country: Greece
city: Heraklion
country: Greece
city: Ioannina
country: Greece
city: Larisa
country: Greece
city: Patras
country: Greece
city: Thessaloniki
country: Greece
city: Thessaloniki
country: Greece
city: Thessaloniki
country: Greece
city: Thessaloniki
country: Greece
city: Cork
country: Ireland
city: Dublin
country: Ireland
city: Firenze
country: Italy
city: Monserrato
country: Italy
city: Napoli
country: Italy
city: Palermo
country: Italy
city: Potenza
country: Italy
city: Reggio Emilia
country: Italy
city: Roma
country: Italy
city: Den Helder
country: Netherlands
city: Enschede
country: Netherlands
city: Leeuwarden
country: Netherlands
city: Vlissingen
country: Netherlands
city: Zwolle
country: Netherlands
city: Haugesund
country: Norway
city: Levanger
country: Norway
city: Lillehammer
country: Norway
city: Tromsø
country: Norway
city: Trondheim
country: Norway
city: A Coruña
country: Spain
city: Alicante
country: Spain
city: Asturias
country: Spain
city: Barakaldo
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Burgos
country: Spain
city: Las Palmas de Gran Canaria
country: Spain
city: Las Palmas de Gran Canaria
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Pamplona
country: Spain
city: Valencia
country: Spain
city: Valladolid
country: Spain
city: Vitoria-Gasteiz
country: Spain
city: Vizcaya
country: Spain
city: Zaragoza
country: Spain
city: Eskilstuna
country: Sweden
city: Växjö
country: Sweden
city: Örebro
country: Sweden
city: Östersund
country: Sweden
city: Bern
country: Switzerland
city: Zürich
country: Switzerland
city: Zürich
country: Switzerland
city: Aberdeen
country: United Kingdom
city: Avon
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Greater Manchester
country: United Kingdom
city: Harrow
country: United Kingdom
city: Huddersfield
country: United Kingdom
city: Leeds
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Merseyside
country: United Kingdom
city: Newcastle upon Tyne
country: United Kingdom
city: Oxford
country: United Kingdom
city: Portsmouth
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Southampton
country: United Kingdom
city: Truro
country: United Kingdom
city: Wigan
country: United Kingdom
Study officials:
affiliation: Abbott
name: Beverly Paperiello
role: STUDY_DIRECTOR
References:
citation: Rudwaleit M, Van den Bosch F, Kron M, Kary S, Kupper H. Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy. Arthritis Res Ther. 2010;12(3):R117. doi: 10.1186/ar3054. Epub 2010 Jun 16.
citation: Rudwaleit M, Claudepierre P, Kron M, Kary S, Wong R, Kupper H. Effectiveness of adalimumab in treating patients with ankylosing spondylitis associated with enthesitis and peripheral arthritis. Arthritis Res Ther. 2010;12(2):R43. doi: 10.1186/ar2953. Epub 2010 Mar 15.
citation: Rudwaleit M, Claudepierre P, Wordsworth P, Cortina EL, Sieper J, Kron M, Carcereri-De-Prati R, Kupper H, Kary S. Effectiveness, safety, and predictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis. J Rheumatol. 2009 Apr;36(4):801-8. doi: 10.3899/jrheum.081048. Epub 2009 Feb 27.
citation: Rudwaleit M, Rodevand E, Holck P, Vanhoof J, Kron M, Kary S, Kupper H. Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis. 2009 May;68(5):696-701. doi: 10.1136/ard.2008.092585. Epub 2008 Jul 28.