Dose-ranging Study With GLPG0634 in Methotrexate-refractory Active Rheumatoid Arthritis Patients

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01668641
• Other study ID #: GLPG0634-CL-202
• Status: Completed
• Phase: Phase 2
• First received: August 14, 2012
• Last updated: June 26, 2013
• Start date: May 2012
• Est. completion date: October 2012

Study information

• Verified date: June 2013
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Moldova: Ministry of HealthRussia: Ministry of Health of the Russian FederationUkraine: State Pharmacological Center - Ministry of HealthHungary: National Institute of Pharmacy
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: October 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• GLPG0634

• Placebo

Locations

Country	Name	City	State
Hungary	Budai Irgalamsrendi Korhaz, II. Reumatologia Osztaly	Budapest
Hungary	Orszagos Reumatologiai es Fizioterapias Intezet, I. Reumatologia Osztaly	Budapest
Hungary	Markhot Ferenc Korhaz, Reumatologiai Osztaly	Eger
Hungary	Pest Megyei Flor Ferenc Korhaz, Reumatologiai es Fizioterapias Osztaly	Kistarcsa
Moldova, Republic of	IMSP Institutel de Cardiologie	Chisinau
Russian Federation	State Healthcare Institution of city Moscow 'City Clinical Hospital #7'	Moscow
Russian Federation	State Healthcare Institution 'Ryazan Regional Cardiology Dispensary'	Ryazan
Russian Federation	Saint-Petersburg State Healthcare Institution 'City Hospital #26'	Saint-Petersburg
Russian Federation	Saint-Petersburg State Healthcare Institution 'City Mariinskiy Hospital'	Saint-Petersburg
Russian Federation	Municipal Clinical Healthcare Institution 'Medical-Sanitary Unit of Novoyaroslavskiy Oil Refinery'	Yaroslavl
Ukraine	Chernivtsi Regional Clinical Hospital	Chernivtsi
Ukraine	State Institution 'Institute of Urgent and Recovery Surgery n.a. V.K. Gusaka' of AMS of Ukraine	Donetsk
Ukraine	Communal Institution of Healthcare	Kharkiv
Ukraine	Institution of Therapy of AMS of Ukraine	Kharkiv
Ukraine	State Institution 'Institute of Microbiology and Immunology of AMS of Ukraine'	Kharkiv
Ukraine	State Institution 'Republican Clinical Hospital of MoH of Ukraine'	Kiev
Ukraine	Lutsk City Clinical Hospital	Lutsk
Ukraine	Vinnytsa Regional Clinical Hospital	Vinnytsa
Ukraine	Zaporizhzhia Regional Clinical Hospital	Zaporizhzhia

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

Hungary,  Moldova, Republic of,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of patients with an ACR20 score at Week 4 as a measure of efficacy	To preliminary evaluate the efficacy of GLPG0634 compared to placebo in terms of the proportion of subjects achieving an ACR20 response at Week 4	Week 4 (end of treatment visit)	No
Secondary	The number of patients with ACR20/50/70 response, time to response and DAS28 score at every visit as a measure of efficacy	To evaluate the efficacy of GLPG0634 compared to placebo in terms of ACR response criteria at every visit (ACR20, ACR50, ACR70), time to response, and disease status (DAS28[C-reactive protein, CRP]	From Day -1 up to end of treatment visit (week 4)	No
Secondary	The number of patients with adverse events, abnormal lab tests, vital signs and ECG as a measure of safety and tolerability	To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of adverse events (AEs), laboratory test abnormalities, vital signs and electrocardiogram (ECG)	From screening up to 10 days after last dose	Yes
Secondary	The plasma levels of GLPG0634 as a measure of PK	To characterize the pharmacokinetics (PK) of GLPG0634 by measuring the amount of GLPG0634 in the plasma	Week 1, week 2 and week 4 visits	No
Secondary	The plasma levels of GLPG0634 and MTX as a measure of PK	To explore the potential interaction of GLPG0634 on MTX by assessing steady state PK in an 8-hour sampling at Day -1 and at Week 2 or Week 4 visit in a subset of patients	Day -1 and Week 2 or 4 visit (8 hour-sampling)	No
Secondary	The levels of immune- and inflammation-related parameters in plasma as a measure of PD	To characterize the pharmacodynamics (PD) of GLPG0634 by measuring the levels of immune- and inflammation-related parameters in plasma	Day -1, Week 1, week 2 and week 4 visits	No