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Dose-finding Study of GLPG0634 as Monotherapy in Active Rheumatoid Arthritis (RA) Patients (DARWIN2)

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ClinicalTrials.gov Identifier: NCT01894516
Recruitment Status : Completed
First Posted : July 10, 2013
Last Update Posted : May 17, 2016
Sponsor:
Information provided by (Responsible Party):
Galapagos NV

Tracking Information
First Submitted Date  ICMJE July 4, 2013
First Posted Date  ICMJE July 10, 2013
Last Update Posted Date May 17, 2016
Study Start Date  ICMJE July 2013
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2013)
Percentage of subjects achieving an American College of Rheumatology (ACR)20 response at Week 12 [ Time Frame: Baseline - Week 12 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01894516 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2013)
  • Percentage of subjects achieving an ACR20 response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving an ACR50 response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving an ACR70 response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving an ACR-N response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving a Disease Activity Score on 28 joints and c-reactive protein (DAS28(CRP)) at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • Percentage of subjects achieving an ACR/European League Against Rheumatism (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 Clinical Disease Activity Index/Simplified Disease Activity Index (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 Subject's Disability (based on the Health Assessment Questionnaire-Disability Index (HAQ-DI) scores) at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  • The number of subjects with adverse events (AEs), abnormal lab tests, vital signs and electrocardiogram (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 AEs, laboratory test abnormalities, vital signs and ECG
  • The plasma levels of GLPG0634 and its metabolite as a measure of pharmacokinetics (PK) [ Time Frame: Week 4, 12 and 24 ]
    To characterize the 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 pharmacodynamics (PD) [ Time Frame: Baseline, Week 1, 4, 12 and 24 ]
    To characterize the 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 Monotherapy in Active Rheumatoid Arthritis (RA) Patients (DARWIN2)
Official Title  ICMJE Randomized, Double-blind, Placebo-controlled, Multicenter, Phase IIb Dose Finding Study of GLPG0634 Administered for 24 Weeks as Monotherapy to Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate (MTX) Alone
Brief Summary
  • 280 patients suffering from active rheumatoid arthritis who have an inadequate response to methotrexate will be evaluated for improvement of disease activity (efficacy) when taking GLPG0634 as monotherapy (3 different doses - 50mg, 100mg and 200mg once daily) 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 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, all subjects on placebo and the subjects on the 50 mg dose who have not achieved 20% improvement in swollen joint count (SJC66) and tender joint count (TJC68) will be assigned (automatically via interactive web response system (IWRS)) to 100 mg q.d. in a blinded fashion and will continue treatment 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 50mg QD
    2 capsules of 25mg GLPG0634 in the morning
    Intervention: Drug: GLPG0634
  • Experimental: GLPG0634 100mg QD
    2 capsules of 50mg GLPG0634 in the morning
    Intervention: Drug: GLPG0634
  • Experimental: GLPG0634 200mg QD
    2 capsules of 100mg GLPG0634 in the morning
    Intervention: Drug: GLPG0634
  • Placebo Comparator: Placebo
    2 placebo capsules in the morning
    Intervention: Drug: Placebo
Publications * Kavanaugh A, Kremer J, Ponce L, Cseuz R, Reshetko OV, Stanislavchuk M, Greenwald M, Van der Aa A, Vanhoutte F, Tasset C, Harrison P. Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2). Ann Rheum Dis. 2017 Jun;76(6):1009-1019. doi: 10.1136/annrheumdis-2016-210105. Epub 2016 Dec 19.

*   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: December 14, 2014)
287
Original Estimated Enrollment  ICMJE
 (submitted: July 9, 2013)
280
Actual Study Completion Date  ICMJE July 2015
Actual Primary Completion Date April 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 shown an inadequate response in terms of either lack of efficacy or toxicity to MTX,
  • have agreed to be washed out from MTX for a period of at least 4 weeks before or during the Screening period.

Exclusion Criteria:

  • current therapy with any non-biological disease modifying anti-rheumatic drug (DMARD), with the exception of antimalarials, which must be at a stable dose for at least 12 weeks prior to Screening,
  • current or previous RA treatment with a biologic DMARD, with the exception of biologic DMARDs: administered in a single clinical study setting, and; more than 6 months prior to Screening (12 months for rituximab or other B cell depleting agents), and; 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,   Bulgaria,   Chile,   Colombia,   Germany,   Guatemala,   Hungary,   Latvia,   Mexico,   Moldova, Republic of,   New Zealand,   Poland,   Romania,   Russian Federation,   Spain,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01894516
Other Study ID Numbers  ICMJE GLPG0634-CL-204 (DARWIN2)
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