Clinical trial NCT00525213: Study to Evaluate the Efficacy and Safety of Orally Administered Rob 803 When Added to Methotrexate
Official title: A Phase II, Randomised, Double-blind, International, Multicentre, Placebo-controlled, Dose-ranging, Parallel-group Study to Evaluate the Efficacy and Safety of Orally Administered Rob 803 When Added to Stable Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Lead sponsor: OxyPharma
Sponsor class: INDUSTRY
First posted: 2007-09-05
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the efficacy (ACR20) of Rob 803 administered orally once daily for 12 weeks in combination with a stable dose of methotrexate in subjects with moderate or severe active RA.

Detailed description: Rheumatoid arthritis (RA) is a common, chronic, disabling systemic autoimmune disease in which inflammation of the joint lining (synovium) occurs when the body's tissues are attacked by the immune system. The joint inflammation begins in the synovium and slowly destroys the cartilage, narrowing the joint and eventually damaging the bone. A large amount of inflammatory mediators or rheumatoid factors are synthesised in the joint which accelerate proliferation and differentiation of immune cells further to amplify the autoimmune reaction. A widely accepted model has emerged in which the presence of inflammation in established RA is driven by interactions between T cells, macrophages, and fibroblasts in an abnormal microenvironment.

Rheumatoid arthritis has an annual incidence of approximately 0.2 per 1000 in males and 0.4 per 1000 in females. In general, higher rates have been reported in the USA than in European populations. The incidence of RA increases with age until the mid 70s. A prevalence of 0.5-1% is reported in diverse populations world-wide.

Treatments for RA focus on relieving pain, reducing inflammation, slowing or stopping joint damage, and improving patients' well being and ability to function. Current therapies include non-steroidal anti-inflammatory drugs (NSAIDs) which target the clinical features of the disease to alleviate the pain and swelling that accompany RA, disease-modifying anti-rheumatic drugs (DMARDs) which target the actual cause of the disease and biological agents which are genetically engineered to target and modify the autoimmune response. Non-steroidal anti-inflammatory drugs are effective in managing the symptoms of RA, but are limiting as they cannot suppress progression of the disease. First line treatment on confirmation of RA is the use of DMARDs, supported by pain relief medication.

Biologic agents (TNF antagonists, anti B-cell agents and anti-interleukins) have proven effective in RA symptoms management. TNF antagonists have become an important therapeutic option in the treatment of advanced RA.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with RA based on the ARA 1987 revised criteria at least 16 weeks prior to study enrolment, Day 0
* Have an ACR global functional status class of 1 to 3
* Have active disease, defined as the presence of 6 swollen joints and 6 tender joints in a 44 joint examination
* Have a CRP level at screening of ≥ 1.5 mg/dL
* Have been taking oral or parenteral methotrexate (15 mg weekly or above), have been using methotrexate for at least 16 weeks (up to Day 0 of study), and have been on a stable dose for at least 8 weeks, up to Day 0.

Exclusion Criteria:

* Arthritis onset prior to 16 years old
* Any of the following infections:
* Known or acute infection that may affect CRP levels
* Active tuberculosis
* Known chronic infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) including positive serology
* Ongoing systemic inflammatory condition which may interfere with the results of clinical or laboratory tests planned in the study (eg, systemic lupus erythematosus or any other systemic rheumatic disease other than RA)

Primary outcomes:
measure: To evaluate the efficacy (ACR20) of Rob 803 administered orally once daily for 12 weeks in combination with a stable dose of methotrexate in subjects with moderate or severe active RA.
timeFrame: 12 weeks
Secondary outcomes:
measure: Evaluate the safety of Rob 803 administered orally once daily in combination with a stable dose of methotrexate in subjects with moderate or severe active RA
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: CUB Hôpital Erasme Université Libre de Bruxelles Service de Rhumatologie
city: Gent
country: Belgium
facility: AZ Sint-Lucas Gent Reumatologie
city: Hasselt
country: Belgium
facility: Reumainstituut Anne Frankplein 17
city: Pleven
country: Bulgaria
facility: Clinic of Cardiology and Rheumatology UMHAT "Dr. Georgi Stranski"
city: Ploviv
country: Bulgaria
facility: UMHAT sveti georgi
city: Sofia
country: Bulgaria
facility: Clinic of Rheumatology MHAT "Sveti Ivan Rilski"
city: Sofia
country: Bulgaria
facility: Department of Rheumocardiology, Pulmonology and General Therapy
city: Varna
country: Bulgaria
facility: Clinic of Rheumatology, UMHAT "Sveta Marina",
city: Tbilisi
country: Georgia
facility: Academician V Tsitlanadze Scientific-Practical Centre of Rheumatolgoy
city: Tbilisi
country: Georgia
facility: Rheumatology Department Cemotherapy and Immunotherapy Clinical
city: Liepaja
country: Latvia
facility: D Saulites-Kandevicas gimenes arsta prakse
state: Aldaru iela 8,
city: Valmiera
country: Latvia
facility: Salenieces arsta reimatologa prakse
city: Kaunas
country: Lithuania
facility: Rheumatology Clinic Hospital of Kaunas University of Medicine
city: Siauliai
country: Lithuania
facility: Department of Therapy and diagnostics Siauliai district hospital
city: Vilnius
country: Lithuania
facility: Center of Reumathology Vilnius University hospital Santariskiu Clinics
city: Bialystok
country: Poland
facility: Centrum Miriada Prywatny Gabinet
city: Bytom
country: Poland
facility: Szpital Specjalistyczny Nr 1 Oddzial Reumatologii i Rehabilitacji
city: Poznan
country: Poland
facility: Poznanski Osrodek Medyczny Nova Med
city: Szczecin
country: Poland
facility: Indywidualna Specjalistyczna Praktyka
city: Warszawa
country: Poland
facility: Centrum Medyczne Osteomed
city: Wroclaw
country: Poland
facility: Prywatny Gabinet Lekarski
city: Bucharest
country: Romania
facility: "Sf. Maria" Clinical Hospital
city: Bucharest
country: Romania
facility: "Dr. I. Cantacuzino" Clinical Hospital
city: Cluj Napoca
country: Romania
facility: Emergency Clinical County Hospital
city: Cluj-Napoca,
country: Romania
facility: "Dr. Constantin Papilian"
city: Lasi
country: Romania
facility: Rehabilitation Clinical Hospital
city: Sibiu
country: Romania
facility: Emergency County Hospital
city: Belgrade
country: Serbia
facility: Institute of Rheumatology Belgrade
city: Niska Banja
country: Serbia
facility: Institute for Prevention, Treatment and Rehabilitation of Rheumatic and Cardiovascular Diseases
city: Stockholm
country: Sweden
facility: Reumatologiska kliniken Karolinska Sjukhuset
city: Leeds
country: United Kingdom
facility: Musculo Skeletal dept Chapel Allerton Hospital
city: Newport
country: United Kingdom
facility: Vectasearch Clinic Ltd St Mary's Hospital
city: North Shields
country: United Kingdom
facility: Rheumatology Unit North Tyneside District General Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Lars Klareskog, Professor
role: PRINCIPAL_INVESTIGATOR
References: