Clinical trial NCT01668641: Dose-ranging Study With GLPG0634 in Methotrexate-refractory Active Rheumatoid Arthritis Patients
Official title: Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II Study to Compare Four Dose Regimens of GLPG0634 Versus Placebo, in Combination With Methotrexate, Administered for 4 Weeks in the Treatment of Subjects With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Methotrexate insufficient responders
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2012-08-20
Enrollment: 91
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: * Ninety patients suffering from active rheumatoid arthritis despite continued treatment with methotrexate will be evaluated for improvement of disease activity when taking GLPG0634 (4 different doses will be evaluated) or matching placebo for 4 weeks.
* During the course of the study, patients will also be examined for any side effects that may occur, and the amount of GLPG0634 present in the blood as well as the effects of GLPG0634 on disease- and mechanism of action-related parameters in the blood will be determined.


Eligibility criteria: Inclusion Criteria:

* Have active RA as shown by five or more swollen joints (from the 66-joint count), five or more tender joints (from 68-joint count), and a serum CRP ≥1.0 mg/dL;
* Have received methotrexate for 12 weeks or longer and at a stable dose of 7.5 to 25 mg/week for at least 4 weeks prior to screening and willing to continue on this regimen for the duration of the study;
* If taking oral steroids, these should be at a dose ≤10 mg/day of prednisone or prednisone equivalent and stable for at least 4 weeks prior to screening;
* If taking non-steroidal anti-inflammatory drugs (NSAIDs), these must be at a stable dose for at least 2 weeks prior to screening;
* Female subjects must have a negative pregnancy test unless they are surgically sterile or have been post-menopausal for at least one 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 at least 12 weeks after the last dose of study drug.
* Sexually active men must agree to use a medically acceptable form of contraception during the study and continue its use for at least 3 months after the last dose of study drug; and
* Able and willing to sign the informed consent prior to screening evaluations and agree to schedule of assessments.

Exclusion Criteria:

* Treatment with disease-modifying antirheumatic drugs (DMARDs), other than background methotrexate;
* Current or previous RA treatment with a biological agent, with the exception of biologics administered in a clinical study setting more than six months prior to screening (12 months for rituximab or other B cell depleting agents);
* Previous treatment at any time with a cytotoxic agent, other than methotrexate, before screening;
* Previous use of the study drug GLPG0634;
* Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to screening;
* Known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug as determined by the Investigator;
* Positive serology for HIV1 or 2 or hepatitis B or C, or any history of hepatitis from any cause with the exception of hepatitis A;
* History of any inflammatory rheumatological disorders other than RA;
* History of tuberculosis (TB) infection

Primary outcomes:
measure: The number of patients with an ACR20 score at Week 4 as a measure of efficacy
timeFrame: Week 4 (end of treatment visit)
Secondary outcomes:
measure: The number of patients with ACR20/50/70 response, time to response and DAS28 score at every visit as a measure of efficacy
timeFrame: From Day -1 up to end of treatment visit (week 4)
measure: The number of patients with adverse events, abnormal lab tests, vital signs and ECG as a measure of safety and tolerability
timeFrame: From screening up to 10 days after last dose
measure: The plasma levels of GLPG0634 as a measure of PK
timeFrame: Week 1, week 2 and week 4 visits
measure: The plasma levels of GLPG0634 and MTX as a measure of PK
timeFrame: Day -1 and Week 2 or 4 visit (8 hour-sampling)
measure: The levels of immune- and inflammation-related parameters in plasma as a measure of PD
timeFrame: Day -1, Week 1, week 2 and week 4 visits
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Budai Irgalamsrendi Korhaz, II. Reumatologia Osztaly
city: Budapest
country: Hungary
facility: Orszagos Reumatologiai es Fizioterapias Intezet, I. Reumatologia Osztaly
city: Eger
country: Hungary
facility: Markhot Ferenc Korhaz, Reumatologiai Osztaly
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz, Reumatologiai es Fizioterapias Osztaly
city: Chisinau
country: Moldova, Republic of
facility: IMSP Institutel de Cardiologie
city: Moscow
country: Russian Federation
facility: State Healthcare Institution of city Moscow 'City Clinical Hospital #7'
city: Ryazan
country: Russian Federation
facility: State Healthcare Institution 'Ryazan Regional Cardiology Dispensary'
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Healthcare Institution 'City Hospital #26'
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Healthcare Institution 'City Mariinskiy Hospital'
city: Yaroslavl
country: Russian Federation
facility: Municipal Clinical Healthcare Institution 'Medical-Sanitary Unit of Novoyaroslavskiy Oil Refinery'
city: Chernivtsi
country: Ukraine
facility: Chernivtsi Regional Clinical Hospital
city: Donetsk
country: Ukraine
facility: State Institution 'Institute of Urgent and Recovery Surgery n.a. V.K. Gusaka' of AMS of Ukraine
city: Kharkiv
country: Ukraine
facility: Communal Institution of Healthcare
city: Kharkiv
country: Ukraine
facility: Institution of Therapy of AMS of Ukraine
city: Kharkiv
country: Ukraine
facility: State Institution 'Institute of Microbiology and Immunology of AMS of Ukraine'
city: Kiev
country: Ukraine
facility: State Institution 'Republican Clinical Hospital of MoH of Ukraine'
city: Lutsk
country: Ukraine
facility: Lutsk City Clinical Hospital
city: Vinnytsa
country: Ukraine
facility: Vinnytsa Regional Clinical Hospital
city: Zaporizhzhia
country: Ukraine
facility: Zaporizhzhia Regional Clinical Hospital
Study officials:
affiliation: Galapagos NV
name: Frédéric Vanhoutte, MD
role: STUDY_DIRECTOR
References:
citation: Vanhoutte F, Mazur M, Voloshyn O, Stanislavchuk M, Van der Aa A, Namour F, Galien R, Meuleners L, van 't Klooster G. Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Filgotinib, a Selective JAK-1 Inhibitor, After Short-Term Treatment of Rheumatoid Arthritis: Results of Two Randomized Phase IIa Trials. Arthritis Rheumatol. 2017 Oct;69(10):1949-1959. doi: 10.1002/art.40186. Epub 2017 Aug 31.