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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01888874




Registration number
NCT01888874
Ethics application status
Date submitted
26/06/2013
Date registered
28/06/2013
Date last updated
17/11/2020

Titles & IDs
Public title
Dose-finding Study of GLPG0634 as add-on to Methotrexate in Active Rheumatoid Arthritis Participants (DARWIN1)
Scientific title
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
Secondary ID [1] 0 0
2012-003635-31
Secondary ID [2] 0 0
GLPG0634-CL-203 (DARWIN1)
Universal Trial Number (UTN)
Trial acronym
DARWIN1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GLPG0634
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - Participants received GLPG0634 matching placebo capsules, orally, twice daily (BID) during Weeks 1 to 12. Participants who were responders (having at least 20 percent [%] improvement on TJC68 and SJC66) remained on placebo while nonresponders were re-randomized to GLPG0634 100 milligram (mg) once daily (QD) or 50 mg BID during Weeks 13 to 24.

Experimental: GLPG0634 50 mg QD - Participants received GLPG0634 50 mg capsules, orally, QD during Weeks 1 to 12. Participants who were responders (having at least 20% improvement on TJC68 and SJC66) remained on 50 mg QD while nonresponders were re-randomized to 100 mg QD during Weeks 13 to 24.

Experimental: GLPG0634 100 mg QD - Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24.

Experimental: GLPG0634 200 mg QD - Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24.

Experimental: GLPG0634 25 mg BID - Participants received GLPG0634 25 mg capsules, orally, BID during Weeks 1 to 12. Participants who were responders (having at least 20% improvement on TJC68 and SJC66) remained on 25 mg BID while nonresponders were re-randomized to 50 mg BID during Weeks 13 to 24.

Experimental: GLPG0634 50 mg BID - Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24.

Experimental: GLPG0634 100 mg BID - Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24.


Treatment: Drugs: GLPG0634
GLPG0634 capsules.

Treatment: Drugs: Placebo
Placebo capsules.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
Percentage of Participants Achieving an ACR20 Response at Week 24
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Percentage of Participants Achieving an ACR50 Response at Weeks 1, 2, 4, 8, 12, and 24
Timepoint [2] 0 0
Weeks 1, 2, 4, 8, 12, and 24
Secondary outcome [3] 0 0
Percentage of Participants Achieving an ACR70 Response at Weeks 1, 2, 4, 8, 12, and 24
Timepoint [3] 0 0
Weeks 1, 2, 4, 8, 12, and 24
Secondary outcome [4] 0 0
ACR N% Improvement (ACR-N) Response at Weeks 1, 2, 4, 8, 12, and 24
Timepoint [4] 0 0
Weeks 1, 2, 4, 8, 12, and 24
Secondary outcome [5] 0 0
Percentage of Participants With Disease Activity Score 28 Joints Corrected for CRP (DAS28 (CRP)) European League Against Rheumatism (EULAR) Response at Weeks 1, 2, 4, 8, 12, and 24
Timepoint [5] 0 0
Weeks 1, 2, 4, 8, 12, and 24
Secondary outcome [6] 0 0
Percentage of Participants Achieving ACR/EULAR Remission at Weeks 2, 4, 8, 12, and 24
Timepoint [6] 0 0
Weeks 2, 4, 8, 12, and 24
Secondary outcome [7] 0 0
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 1, 2, 4, 8, 12, and 24
Timepoint [7] 0 0
Baseline and Weeks 1, 2, 4, 8, 12, and 24
Secondary outcome [8] 0 0
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 1, 2, 4, 8, 12, and 24
Timepoint [8] 0 0
Baseline and Weeks 1, 2, 4, 8, 12, and 24
Secondary outcome [9] 0 0
Change From Baseline in Quality of Life Using the Functional Assessment of Chronic Illness Therapy (FACIT) at Weeks 4, 12, and 24
Timepoint [9] 0 0
Baseline and Weeks 4, 12, and 24
Secondary outcome [10] 0 0
Change From Baseline in Quality of Life Using the Short Form-36 (SF-36) Scores at Weeks 4, 12, and 24
Timepoint [10] 0 0
Baseline and Weeks 4, 12, and 24

Eligibility
Key inclusion criteria
- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/05/2015
Sample size
Target
Accrual to date
Final
599
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Repatriation General Hospital - Daw Park
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Daw Park
Recruitment postcode(s) [4] 0 0
- Woolloongabba
Recruitment outside Australia
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Lutsk

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Galapagos NV
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Participants suffering from active rheumatoid arthritis despite continued treatment with
methotrexate were evaluated for improvement of disease activity (efficacy) when taking
GLPG0634 (3 different doses - 50 milligram [mg], 100 mg and 200 mg daily -, each evaluated as
once daily [QD] and twice daily [BID] regimen) or matching placebo for 24 weeks.

•During the course of the study, patients were also examined for any side effects that could
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) were determined. Also, the effects
of different doses and dose regiments of GLPG0634 administration on participants' disability,
fatigue, and quality of life were evaluated.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01888874
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Galapagos Study Director
Address 0 0
Galapagos NV
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries