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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Galapagos NV
ClinicalTrials.gov Identifier:
NCT01668641
First received: August 14, 2012
Last updated: June 26, 2013
Last verified: June 2013
  Purpose
  • 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.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: GLPG0634
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Galapagos NV:

Primary Outcome Measures:
  • The number of patients with an ACR20 score at Week 4 as a measure of efficacy [ Time Frame: Week 4 (end of treatment visit) ] [ Designated as safety issue: No ]
    To preliminary evaluate the efficacy of GLPG0634 compared to placebo in terms of the proportion of subjects achieving an ACR20 response at Week 4


Secondary Outcome Measures:
  • The number of patients with ACR20/50/70 response, time to response and DAS28 score at every visit as a measure of efficacy [ Time Frame: From Day -1 up to end of treatment visit (week 4) ] [ Designated as safety issue: No ]
    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]

  • The number of patients with adverse events, abnormal lab tests, vital signs and ECG as a measure of safety and tolerability [ Time Frame: From screening up to 10 days after last dose ] [ Designated as safety issue: Yes ]
    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)

  • The plasma levels of GLPG0634 as a measure of PK [ Time Frame: Week 1, week 2 and week 4 visits ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of GLPG0634 by measuring the amount of GLPG0634 in the plasma

  • The plasma levels of GLPG0634 and MTX as a measure of PK [ Time Frame: Day -1 and Week 2 or 4 visit (8 hour-sampling) ] [ Designated as safety issue: No ]
    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

  • The levels of immune- and inflammation-related parameters in plasma as a measure of PD [ Time Frame: Day -1, Week 1, week 2 and week 4 visits ] [ Designated as safety issue: No ]
    To characterize the pharmacodynamics (PD) of GLPG0634 by measuring the levels of immune- and inflammation-related parameters in plasma


Enrollment: 91
Study Start Date: May 2012
Study Completion Date: October 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: capsule, 30mg GLPG0634 once a day
3 capsules of 10 mg once a day
Drug: GLPG0634
Experimental: capsules, 75mg GLPG0634 once a day
3 capsules of 25mg once a day
Drug: GLPG0634
Experimental: capsules, 150mg GLPG0634 once a day
3 capsules of 50mg once a day
Drug: GLPG0634
Experimental: capsules, 300mg GLPG0634 once a day
3 capsules of 100mg once a day
Drug: GLPG0634
Placebo Comparator: capsules, placebo once a day
3 capsules placebo once a day
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01668641

Locations
Hungary
Orszagos Reumatologiai es Fizioterapias Intezet, I. Reumatologia Osztaly
Budapest, Hungary
Budai Irgalamsrendi Korhaz, II. Reumatologia Osztaly
Budapest, Hungary
Markhot Ferenc Korhaz, Reumatologiai Osztaly
Eger, Hungary
Pest Megyei Flor Ferenc Korhaz, Reumatologiai es Fizioterapias Osztaly
Kistarcsa, Hungary
Moldova, Republic of
IMSP Institutel de Cardiologie
Chisinau, Moldova, Republic of
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, Russian Federation
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
Institution of Therapy of AMS of Ukraine
Kharkiv, Ukraine
State Institution 'Institute of Microbiology and Immunology of AMS of Ukraine'
Kharkiv, Ukraine
Communal Institution of Healthcare
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, Ukraine
Sponsors and Collaborators
Galapagos NV
Investigators
Study Director: Frédéric Vanhoutte, MD Galapagos NV
  More Information

No publications provided

Responsible Party: Galapagos NV
ClinicalTrials.gov Identifier: NCT01668641     History of Changes
Other Study ID Numbers: GLPG0634-CL-202
Study First Received: August 14, 2012
Last Updated: June 26, 2013
Health Authority: Moldova: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Ukraine: State Pharmacological Center - Ministry of Health
Hungary: National Institute of Pharmacy

Keywords provided by Galapagos NV:
Methotrexate insufficient responders

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014