Clinical trial NCT01211249: GLPG0259 in Methotrexate-refractory Rheumatoid Arthritis
Official title: Randomized, Double-Blind, Placebo-Controlled, Multicenter, Exploratory Phase II Study to Compare Three Dose Regimens of GLPG0259 vs Placebo, in Combination With Methotrexate, Administered for 12 Weeks to Subjects With Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Methotrexate-refractory
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2010-09-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Part A: 30 patients suffering from active rheumatoid arthritis despite continued treatment with methotrexate will receive once daily two capsules containing either GLPG0259 (25 mg/capsule) or matching placebo, for 12 weeks. In the course of the study the patients will be examined for severity of disease, as well as for any adverse effects that may occur. If needed, dosing may be split to one capsule twice daily, or reduced to one capsule of 25 mg.

Part B: If results of Part A suggest test medication to have a therapeutic advantage over placebo and to be well-tolerated, more patients will be recruited for Part B, where various dosages will be assessed. These dosages will be established based on results from Part A.


Eligibility criteria: Inclusion Criteria:

* Must have active RA (≥5 tender or painful joints on motion and ≥5 joints swollen AND a C-reactive protein (CRP) concentration ≥1.5 mg/dL).
* Must have been on methotrexate for ≥6 months at a stable dose of 7.5-25 mg/week for ≥12 weeks, to be continued throughout study;
* If on oral steroids, these should be at a dose ≤10 mg/day of prednisone eq and stable for ≥4 weeks prior to screening;
* If on NSAIDs, these must be at a stable dose for ≥2 weeks prior to screening;
* Women must have negative pregnancy test unless surgically sterile or post-menopausal for ≥1 year;
* Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for ≥12 weeks after the last dose of study drug.
* Informed consent

Exclusion Criteria:

* Must not have received treatment with DMARDs, other than background methotrexate;
* Must not be receiving or have received RA treatment with a biological agent, except if administered in a clinical study ≥six months prior to screening (12 months for rituximab or other B cell depleting agents);
* Must not have received any treatment with a cytotoxic agent, other than methotrexate, before screening (e.g. chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents);
* Must not have received intra-articular or parenteral corticosteroid injection within four weeks prior to screening;
* Must not regularly be using aspirin or any other anti-coagulant medication;
* Must not have a known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug as determined by the Investigator, such as anaphylaxis, requiring hospitalization;
* Must not have positive serology for human immunodeficiency virus (HIV)1 or 2 or hepatitis B or C, or any history of HIV or hepatitis from any cause with the exception of hepatitis A;
* Must not have a history of any inflammatory rheumatological disorders other than RA;
* Must not have undergone (or planned) surgical treatments for RA;
* Must not have symptoms of clinically significant illness other than RA (including but not limited to cardiopulmonary, renal, metabolic, hematologic, or psychiatric disorders) within three months prior to screening;
* Must not have a history of active infections requiring intravenous antibiotics within the past four weeks;
* Must not have a history of malignancy within the past five years (except for basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been treated with no evidence of recurrence);
* Must not have a history of tuberculosis (TB) infection as determined by a positive diagnostic TB test result (defined as a positive QuantiFERON TB Gold test), AND a recent chest radiograph (both posterior-anterior and lateral views), read by a qualified radiologist, with evidence of current active TB or old inactive TB.
* Must not have been administered a live vaccine within four weeks prior to screening;
* Must not have participated in any investigational drug/device clinical study within four weeks prior to screening, in biological agents clinical studies within six months prior to screening, and B cell-depleting agent clinical studies within 12 months prior to screening;
* Must not have a history within the previous two years or current evidence of drug or alcohol abuse;
* Must not have any condition or circumstances which in the opinion of the Investigator may make a subject unlikely or unable to complete the study or comply with study procedures and requirements, or may pose a risk to the patient's safety.

Primary outcomes:
measure: Efficacy
timeFrame: 12 weeks
Secondary outcomes:
measure: Efficacy
timeFrame: intermediate timepoints for 12 weeks
measure: Safety
timeFrame: 12 weeks
measure: Pharmacokinetics
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: KU Leuven
city: Sijsele-Damme
country: Belgium
facility: AZ Alma
city: Leiden
country: Netherlands
facility: UMC Leiden
city: Kraków
country: Poland
facility: Specjalistyczne Centrum Medyczne NZOZ NOWOMED
city: Warszawa
country: Poland
facility: "Linea Corporis" - Chirurgia Plastyczna Sp. z o.o.
city: Warszawa
country: Poland
facility: Mokotowskie Centrum Osteoporozy S.C.
city: Wrocław
country: Poland
facility: Synexus SCM Sp. z o.o.
city: Wrocław
country: Poland
facility: Akademia Medyczna im. Piastów Śląskich we Wroclawiu Katedra i Klinika Reumatologii i Chorób Wewnętrznych UM we Wrocławiu
city: Moscow
country: Russian Federation
facility: State Educational Institution of Higher Professional Education "Moscow State Medico-Stomatological University of Roszdrav" State Healthcare Institution of City Moscow "City Clinical Ordena Trudovogo Krasnogo Znameny Hospital #23 n.a. "Medsantrud"
city: Moscow
country: Russian Federation
facility: State Healthcare Institution of city Moscow "City Clinical Ordena Trudovogo Krasnogo Znameny Hospital #23 n.a. "Medsantrud"
city: Moscow
country: Russian Federation
facility: State Educational Institution of Higher Professional Education "Russian State Medical University of Roszdrav" State Healthcare Institution of City Moscow "City Clinical Hospital #15 n.a. O.M. Filatov"
city: Moscow
country: Russian Federation
facility: State Healthcare Institution of City Moscow "City Clinical Hospital #4"
city: Moscow
country: Russian Federation
facility: State Healthcare Institution of City Moscow "City Clinical Hospital #7"
city: Moscow
country: Russian Federation
facility: Institution Russian Academy of Medical Sciences Scientific Research Institution of Rheumatology RAMN
city: Moscow
country: Russian Federation
facility: State Healthcare Institution of City Moscow "City Clinical Hospital #1 n.a. Pirogov"
city: Moscow
country: Russian Federation
facility: State Educational Institution of Higher Professional Education "Moscow State Medico-Stomatological University of Roszdrav" at the State Healthcare Institution of city Moscow "City Clinical Ordena Trudovogo Krasnogo Znameny hospital #23 n.a. "M
city: Moscow
country: Russian Federation
facility: Saint-Petersburg State Healthcare Institution "City Hospital #26"
city: St Petersburg
country: Russian Federation
facility: Saint-Petersburg State Healthcare Institution "City Pokrovskaya Hospital"
city: St Petersburg
country: Russian Federation
facility: Institution of Russian Academy of Sciences Saint-Petersburg Clinical Hospital RAN
city: St-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Healthcare Institution "City Mariinskiy Hospital"
city: St. Petersburg
country: Russian Federation
facility: State Educational Institution of Higher Professional Education "Saint-Petersburg State Pediatric Medical Academy of Roszdrav"
city: Chernivtsi
country: Ukraine
facility: Chernivtsi Regional Clinical Hospital
city: Donetsk
country: Ukraine
facility: Donetsk City Hospital No5
city: Kharkiv
country: Ukraine
facility: Kharkiv City Clinical Hospital No.27
city: Kharkiv
country: Ukraine
facility: Kharkiv City Clinical Hospital No.8
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital No.3
city: Kyiv
country: Ukraine
facility: Central Pool-type Clinical Hospital MoH of Ukraine
city: Kyiv
country: Ukraine
facility: Institute of Gerontology AMS of Ukraine
city: Simferopol
country: Ukraine
facility: University Clinic, Crimean Medical University
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Hospital
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhia Regional Hospital
Study officials:
affiliation: Galapagos NV
name: Johan Beetens, PhD
role: STUDY_DIRECTOR
References:
citation: Westhovens R, Keyser FD, Rekalov D, Nasonov EL, Beetens J, Van der Aa A, Wigerinck P, Namour F, Vanhoutte F, Durez P. Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the treatment of rheumatoid arthritis: a phase II, randomised, double-blind, placebo-controlled, multicentre trial. Ann Rheum Dis. 2013 May;72(5):741-4. doi: 10.1136/annrheumdis-2012-202221. Epub 2012 Nov 17.