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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

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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: GLPG0634 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 287 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2013
Actual Primary Completion Date : April 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GLPG0634 50mg QD
2 capsules of 25mg GLPG0634 in the morning
Drug: GLPG0634
Experimental: GLPG0634 100mg QD
2 capsules of 50mg GLPG0634 in the morning
Drug: GLPG0634
Experimental: GLPG0634 200mg QD
2 capsules of 100mg GLPG0634 in the morning
Drug: GLPG0634
Placebo Comparator: Placebo
2 placebo capsules in the morning
Drug: Placebo



Primary Outcome Measures :
  1. Percentage of subjects achieving an American College of Rheumatology (ACR)20 response at Week 12 [ Time Frame: Baseline - Week 12 ]

Secondary Outcome Measures :
  1. Percentage of subjects achieving an ACR20 response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  2. Percentage of subjects achieving an ACR50 response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  3. Percentage of subjects achieving an ACR70 response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  4. Percentage of subjects achieving an ACR-N response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  5. 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 ]
  6. 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 ]
  7. Percentage of subjects achieving a EULAR response at every visit from Week 1 to 24 [ Time Frame: Baseline to Week 24 ]
  8. 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 ]
  9. Change versus Baseline in functional assessment of chronic illness therapy (FACIT) at Weeks 4, 12 and 24 [ Time Frame: Baseline to Week 24 ]
  10. Change versus Baseline in Short Form-36 scores (Quality of Life assessment) at Weeks 4, 12 and 24 [ Time Frame: Baseline to Week 24 ]
  11. 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 ]
  12. 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

  13. 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

  14. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01894516


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Sponsors and Collaborators
Galapagos NV
Investigators
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Study Director: Pille Harrison, MD Galapagos NV

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Galapagos NV
ClinicalTrials.gov Identifier: NCT01894516     History of Changes
Other Study ID Numbers: GLPG0634-CL-204 (DARWIN2)
First Posted: July 10, 2013    Key Record Dates
Last Update Posted: May 17, 2016
Last Verified: July 2015

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases