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Dose-finding Study of GLPG0634 as add-on to Methotrexate in Active Rheumatoid Arthritis Patients (DARWIN1) (DARWIN1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01888874
Recruitment Status : Completed
First Posted : June 28, 2013
Last Update Posted : May 17, 2016
Sponsor:
Information provided by (Responsible Party):
Galapagos NV

Tracking Information
First Submitted Date  ICMJE June 26, 2013
First Posted Date  ICMJE June 28, 2013
Last Update Posted Date May 17, 2016
Study Start Date  ICMJE July 2013
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2013)
Percentage of subjects achieving an ACR20 response at Week 12 [ Time Frame: Baseline - Week 12 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2013)
  • Percentage of subjects achieving ACR20 response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving ACR50 response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving ACR70 response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving ACR-N response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving DAS28(CRP) score at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving an ACR/EULAR remission at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving a EULAR response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving a CDAI/SDAI response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Change versus Baseline in functional assessment of chronic illness therapy [FACIT] at Weeks 4, 12 and 24 [ Time Frame: Baseline to Week 24 ]
  • Change versus Baseline in Short Form-36 scores (Quality of Life assessment) at Weeks 4, 12, and 24 [ Time Frame: Baseline to Week 24 ]
  • Change versus Baseline in Subjects's Disability (based on the HAQ-DI questionnaire scores) at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • The number of subjects with adverse events, abnormal lab tests, vital signs and ECG [ Time Frame: From screening up to 10 days after last dose ]
    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 and its metabolite as a measure of PK [ Time Frame: Week 4, 12 and 24 ]
    To characterize the pharmacokinetics (PK) of GLPG0634 and its metabolite by measuring the amount in the plasma
  • The change versus Baseline in levels of immune- and inflammation-related parameters in whole blood and serum as a measure of PD [ Time Frame: Baseline, Week 1, 4, 12 and 24 ]
    To characterize the pharmacodynamics (PD) of GLPG0634 and its metabolite by measuring the levels of immune- and inflammation-related parameters in whole blood and serum
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-finding Study of GLPG0634 as add-on to Methotrexate in Active Rheumatoid Arthritis Patients (DARWIN1)
Official Title  ICMJE Randomized, Double-blind, Placebo-controlled, Multicenter, Phase IIb Dose Finding Study of GLPG0634 Administered for 24 Weeks in Combination With Methotrexate to Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Alone
Brief Summary
  • 595 patients suffering from active rheumatoid arthritis despite continued treatment with methotrexate will be evaluated for improvement of disease activity (efficacy) when taking GLPG0634 (3 different doses - 50mg, 100mg and 200mg daily -, each evaluated as QD and BID regimen) or matching placebo for 24 weeks.
  • During the course of the study, patients will also be examined for any side effects that may occur (safety and tolerability), and the amount of GLPG0634 present in the blood (Pharmacokinetics) as well as the effects of GLPG0634 on disease- and mechanism of action-related parameters in the blood (Pharmacodynamics) will be determined. Also, the effects of different doses and dose regiments of GLPG0634 administration on subjects' disability, fatigue, and quality of life will be evaluated.
Detailed Description
  • Treatment duration will be 24 weeks in total.
  • However, at Week 12, subjects on placebo who have not achieved a 20% improvement in swollen joint count(SJC66) and tender joint count (TJC68) will be re-randomized (automatically via interactive voice/web response [IXRS]) to treatment to receive GLPG0634 100 mg q.d. or 50 mg b.i.d. doses in a blinded fashion, subjects on 50 mg q.d. who have not achieved a 20% improvement in SJC66 and TJC68 will be assigned to 100 mg q.d. and subjects on 25 mg b.i.d. who have not achieved a 20% improvement in SJC66 and TJC68 will be assigned to 50 mg b.i.d. All will continue the study until Week 24.
  • Subjects in the other groups will maintain their randomized treatment until Week 24.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: GLPG0634
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: GLPG0634 25mg BID
    1 capsule of 25 mg GLPG0634 and 1 placebo capsule both in the morning and in the evening
    Interventions:
    • Drug: GLPG0634
    • Drug: Placebo
  • Experimental: GLPG0634 50mg QD
    1 capsule of 50 mg GLPG0634 and 1 placebo capsule in the morning and 2 placebo capsules in the evening
    Interventions:
    • Drug: GLPG0634
    • Drug: Placebo
  • Experimental: GLPG0634 50mg BID
    1 capsule of 50 mg GLPG0634 and 1 placebo capsule both in the morning and in the evening
    Interventions:
    • Drug: GLPG0634
    • Drug: Placebo
  • Experimental: GLPG0634 100mg QD
    1 capsule of 100 mg GLPG0634 and 1 placebo capsule in the morning and 2 placebo capsules in the evening
    Interventions:
    • Drug: GLPG0634
    • Drug: Placebo
  • Experimental: GLPG0634 100mg BID
    1 capsule of 100 mg GLPG0634 and 1 placebo capsule both in the morning and in the evening
    Interventions:
    • Drug: GLPG0634
    • Drug: Placebo
  • Experimental: GLPG0634 200mg QD
    2 capsules of 100 mg GLPG0634 in the morning and 2 placebo capsules in the evening
    Interventions:
    • Drug: GLPG0634
    • Drug: Placebo
  • Placebo Comparator: Placebo
    2 placebo capsules both in the morning and in the evening
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 28, 2014)
599
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2013)
595
Actual Study Completion Date  ICMJE June 2015
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • male or female subjects who are ≥18 years of age, on the day of signing informed consent,
  • have a diagnosis of RA since at least 6 months and meeting the 2010 ACR/EULAR criteria of RA and ACR functional class I-III,
  • have ≥6 swollen joints (from a 66 joint count) and

    ≥8 tender joints (from a 68 joint count) at Screening and at Baseline,

  • Screening serum c-reactive protein ≥0.7 x upper limit of laboratory normal range (ULN),
  • have received MTX for ≥6 months and have been on a stable dose (15 to 25 mg/week) of MTX for at least 4 weeks prior to Screening and willing to continue on their current regimen for the duration of the study. Stable doses of MTX as low as 10 mg/week are allowed when there is documented evidence of intolerance or safety issues at higher doses.

Exclusion Criteria:

  • current therapy with any disease-modifying anti-rheumatic drugs (DMARD) other than MTX,
  • current or previous RA treatment with a biologic DMARD, with the exception of biologic DMARDs administered in a single clinical study setting more than 6 months prior to Screening (12 months for rituximab or other B cell depleting agents), where the biologic DMARD was effective, and if discontinued, this should not be due to lack of efficacy,
  • previous treatment at any time with a cytotoxic agent, other than MTX, before Screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Bulgaria,   Chile,   Colombia,   Czech Republic,   France,   Germany,   Guatemala,   Hungary,   Israel,   Latvia,   Mexico,   Moldova, Republic of,   New Zealand,   Poland,   Russian Federation,   Spain,   Ukraine,   United States
Removed Location Countries Peru,   Puerto Rico
 
Administrative Information
NCT Number  ICMJE NCT01888874
Other Study ID Numbers  ICMJE GLPG0634-CL-203 (DARWIN1)
2012-003635-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Galapagos NV
Study Sponsor  ICMJE Galapagos NV
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pille Harrison, MD Galapagos NV
PRS Account Galapagos NV
Verification Date July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP