Dose-finding Study of GLPG0634 as add-on to Methotrexate in Active Rheumatoid Arthritis Participants (DARWIN1)
Sponsor
Galapagos NV (Industry)
Overall Status
Completed
CT.gov ID
NCT01888874
Collaborator
(none)
599
142
7
21.9
4.2
0.2
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
-
Treatment duration was 24 weeks in total.
-
However, at Week 12, participants on placebo who did not achieve a 20% improvement in swollen joint count(SJC66) and tender joint count (TJC68) were re-randomized (automatically via interactive voice/web response [IXRS]) to treatment to receive GLPG0634 100 mg QD or 50 mg BID doses in a blinded fashion, participants on 50 mg QD who had not achieved a 20% improvement in SJC66 and TJC68 were assigned to 100 mg QD and participants on 25 mg BID. who did not achieve a 20% improvement in SJC66 and TJC68 were assigned to 50 mg BID. All continued the study until Week 24.
-
Participants in the other groups maintained their randomized treatment until Week 24.
Study Design
Study Type:
Interventional
Actual Enrollment
:
599 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 in Combination With Methotrexate to Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Alone
Actual Study Start Date
:
Jul 17, 2013
Actual Primary Completion Date
:
Feb 18, 2015
Actual Study Completion Date
:
May 14, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: Placebo
Placebo capsules.
|
| 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. |
Drug: GLPG0634
GLPG0634 capsules.
|
| Experimental: GLPG0634 100 mg QD Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. |
Drug: GLPG0634
GLPG0634 capsules.
|
| Experimental: GLPG0634 200 mg QD Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. |
Drug: GLPG0634
GLPG0634 capsules.
|
| 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. |
Drug: GLPG0634
GLPG0634 capsules.
|
| Experimental: GLPG0634 50 mg BID Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. |
Drug: GLPG0634
GLPG0634 capsules.
|
| Experimental: GLPG0634 100 mg BID Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
Drug: GLPG0634
GLPG0634 capsules.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12 [Week 12]
The American College of Rheumatology (ACR) response is a measurement of improvement in multiple disease assessment criteria. The ACR20 response is defined as: 1) ≥ 20% improvement from baseline in SJC66, and 2) ≥ 20% improvement from baseline in tender TJC68, and 3) ≥ 20% improvement from baseline in at least 3 of the following 5 items: 1. Pain visual analog scale (VAS) (taken from the Health Assessment Questionnaire - Disability Index [HAQ-DI]), 2. Patient's Global Assessment of Disease Activity VAS, 3. Physician's Global Assessment of Disease Activity VAS, 4. Total HAQ-DI score, and 5. CRP. Non-responder imputation was used (ie, to impute a missing response, the participant was assumed to be a non-responder).
Secondary Outcome Measures
- Percentage of Participants Achieving an ACR20 Response at Week 24 [Week 24]
ACR20 response was defined as: 1) ≥ 20% improvement from baseline in SJC66, and 2) ≥ 20% improvement from baseline in TJC68, and 3) ≥ 20% improvement from baseline in at least 3 of the following 5 items: 1. Pain VAS (taken from the HAQ-DI), 2. Patient's Global Assessment of Disease Activity VAS, 3. Physician's Global Assessment of Disease Activity VAS, 4. Total HAQ-DI score, and 5. CRP. Non-responder imputation was used.
- Percentage of Participants Achieving an ACR50 Response at Weeks 1, 2, 4, 8, 12, and 24 [Weeks 1, 2, 4, 8, 12, and 24]
ACR50 response was defined as: 1) ≥ 50% improvement from baseline in SJC66, and 2) ≥ 50% improvement from baseline in TJC68, and 3) ≥ 50% improvement from baseline in at least 3 of the following 5 items: 1. Pain VAS (taken from the HAQ-DI) 2. Patient's Global Assessment of Disease Activity VAS 3. Physician's Global Assessment of Disease Activity VAS 4. Total HAQ-DI score 5. CRP. Non-responder imputation was used.
- Percentage of Participants Achieving an ACR70 Response at Weeks 1, 2, 4, 8, 12, and 24 [Weeks 1, 2, 4, 8, 12, and 24]
ACR70 response: 1) ≥ 70% improvement from baseline in SJC66, and 2) ≥ 70% improvement from baseline in TJC68, and 3) ≥ 70% improvement from baseline in at least 3 of the following 5 items: 1. Pain VAS (taken from the HAQ-DI), 2. Patient's Global Assessment of Disease Activity VAS, 3. Physician's Global Assessment of Disease Activity VAS, 4. Total HAQ-DI score, and 5. CRP. Non-responder imputation was used.
- ACR N% Improvement (ACR-N) Response at Weeks 1, 2, 4, 8, 12, and 24 [Weeks 1, 2, 4, 8, 12, and 24]
The ACR-N is the smallest percentage improvement in swollen and tender joints and the median of the remaining 5 core parameters, and is expected to be more sensitive to change than the ACR20, ACR50 or ACR70. It is a number varying between 0 and 100, with higher numbers indicating less severity of symptoms. Last observation carried forward (LOCF) algorithm was used (ie, to impute a missing value, the last preceding nonmissing value was used).
- 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 [Weeks 1, 2, 4, 8, 12, and 24]
DAS28 (CRP) was categorized into EULAR response categories (none, moderate, good) as follows: None = Actual DAS28 (CRP) ≤ 3.2, > 3.2 to ≤ 5.1, or > 5.1 AND Improvement in DAS28 (CRP) from baseline ≤ 6.0 or > 0.6 to ≤ 1.2; Moderate = Actual DAS28 (CRP) ≤ 3.2 AND Improvement in DAS28 (CRP) from baseline > 0.6 to ≤ 1.2, Actual DAS28 (CRP) > 3.2 to ≤ 5.1 or > 5.1 AND Improvement in DAS28 (CRP) from baseline > 1.2, or Actual DAS28 (CRP) > 3.2 to ≤ 5.1 AND Improvement in DAS28 (CRP) from baseline > 0.6 to ≤ 1.2; Good = Actual DAS28 (CRP) ≤ 3.2 AND Improvement in DAS28 (CRP) from baseline > 1.2. LOCF algorithm was used.
- Percentage of Participants Achieving ACR/EULAR Remission at Weeks 2, 4, 8, 12, and 24 [Weeks 2, 4, 8, 12, and 24]
A participant's disease activity status can be defined as being in remission when scores on the TJC28, SJC28, CRP (actual value in mg/dL) and Patient Global Assessment of Disease Activity (cm) are all ≤ 1. Non-responder imputation was used.
- Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 1, 2, 4, 8, 12, and 24 [Baseline and Weeks 1, 2, 4, 8, 12, and 24]
The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, Patient Global Assessment of Disease Activity (in cm), Physician's Global Assessment of Disease Activity (in cm), and CRP (mg/dL). The SDAI was categorized as follows: • High disease activity: SDAI > 26 • Moderate disease activity: 11 to 26 • Low disease activity: 3.3 to 11 • Remission: ≤ 3.3. LOCF algorithm was used. The SDAI total score ranges from 0 to approximately 86.
- Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 1, 2, 4, 8, 12, and 24 [Baseline and Weeks 1, 2, 4, 8, 12, and 24]
The CDAI is the SDAI modified to exclude CRP and is the sum of the 4 outcome parameters: TJC28, SJC28, Patient Global Assessment of Disease Activity (in cm), and Physician's Global Assessment of Disease Activity (in cm). The CDAI was be categorized as follows: • High disease activity: > 22 • Moderate disease activity: 10 to 22 • Mild disease activity: 2.8 to 10 • Remission: ≤ 2.8. LOCF algorithm was used. The CDAI total score ranges from 0 to approximately 76.
- Change From Baseline in Quality of Life Using the Functional Assessment of Chronic Illness Therapy (FACIT) at Weeks 4, 12, and 24 [Baseline and Weeks 4, 12, and 24]
FACIT-Fatigue scale is a 13-item questionnaire, each scored on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated that are scored reversely), the greater the fatigue. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score), with a higher score indicating a better quality of life. LOCF algorithm was used.
- Change From Baseline in Quality of Life Using the Short Form-36 (SF-36) Scores at Weeks 4, 12, and 24 [Baseline and Weeks 4, 12, and 24]
The SF-36 is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores were computed based on weighted combinations of the 8 domain scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). LOCF algorithm was used.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rheumatology Associates of North Alabama, PC | Huntsville | Alabama | United States | |
| 2 | Artho Care, Arthritis Care & Research P.C. | Gilbert | Arizona | United States | |
| 3 | Arizona Arthritis & Rheumatology Research PLLC | Phoenix | Arizona | United States | |
| 4 | C.V. Mehta MD Medical Corporation | Hemet | California | United States | |
| 5 | Center for Innovative TherapyDivision of Rheumatology, UCSD | La Jolla | California | United States | |
| 6 | Desert Medical Advances | Palm Desert | California | United States | |
| 7 | Desert Valley Medical Center | Victorville | California | United States | |
| 8 | Infosphere Clinical Research, Inc. | West Hills | California | United States | |
| 9 | RASF Clinical Research Center | Boca Raton | Florida | United States | |
| 10 | Millennium Research | Ormond Beach | Florida | United States | |
| 11 | Lovelace Scientific Resources | Venice | Florida | United States | |
| 12 | Arthritis Center of North GA | Gainesville | Georgia | United States | |
| 13 | Idaho Arthritis Center | Meridian | Idaho | United States | |
| 14 | The Arthritis Center | Springfield | Illinois | United States | |
| 15 | Professional Research Network of Kansas | Wichita | Kansas | United States | |
| 16 | Arthritis Treatment Center | Frederick | Maryland | United States | |
| 17 | Klein and Associates MD | Hagerstown | Maryland | United States | |
| 18 | Private practice | Lansing | Michigan | United States | |
| 19 | Mayo Clinic | Rochester | Minnesota | United States | |
| 20 | Physicians East | Greenville | North Carolina | United States | |
| 21 | Health Research of Oklahoma | Oklahoma City | Oklahoma | United States | |
| 22 | Altoona Center Clinical Research | Duncansville | Pennsylvania | United States | |
| 23 | Austin Rheumatology Research PA | Austin | Texas | United States | |
| 24 | Arthritis Centers of Texas | Dallas | Texas | United States | |
| 25 | Pioneer Research Solutions Inc | Houston | Texas | United States | |
| 26 | Crossroads Clinical Research, LLC | Victoria | Texas | United States | |
| 27 | Seattle Rheumatology Associates, PLLC | Seattle | Washington | United States | |
| 28 | Mountain State Clinical Research | Clarksburg | West Virginia | United States | |
| 29 | Atencion Integral en Reumatologa | Buenos Aires | Argentina | ||
| 30 | Rheumatology OMI | Buenos Aires | Argentina | ||
| 31 | Instituto Reumatologico | Cordoba | Argentina | ||
| 32 | Instituto Medico CER | Quilmes | Argentina | ||
| 33 | Instituto de Asistencia Reumatologia Integral | San Fernando | Argentina | ||
| 34 | Centro Médico Privado de Reumatología | Tucuman | Argentina | ||
| 35 | Royal Prince Alfred Hospital | Camperdown | Australia | ||
| 36 | Monash Medical Centre | Clayton | Australia | ||
| 37 | Repatriation General Hospital | Daw Park | Australia | ||
| 38 | Princess Alexandra Hospital | Woolloongabba | Australia | ||
| 39 | Medical University/ AKH Vienna/ Dep.of Rheumatology 6J | Wien | Austria | ||
| 40 | Cliniques Universitaires St-Luc | Brussels | Belgium | ||
| 41 | Hospital Brugmann | Brussels | Belgium | ||
| 42 | Rheuma Instituut | Hasselt | Belgium | ||
| 43 | AZ Groeninge | Kortrijk | Belgium | ||
| 44 | UZ Leuven | Leuven | Belgium | ||
| 45 | CHU de Liège | Liege | Belgium | ||
| 46 | "Multiprofile Hospital for Active Treatment - Kaspela" LTD | Plovdiv | Bulgaria | ||
| 47 | MHAT Ruse AD | Ruse | Bulgaria | ||
| 48 | Clinic of Rheumatology MHAT | Sofia | Bulgaria | ||
| 49 | Diagnostic Consultative Center "Sveta Anna" LTD | Sofia | Bulgaria | ||
| 50 | National Transport Hospital "Tsar Boris" III | Sofia | Bulgaria | ||
| 51 | Rheumatology Clinic | Sofia | Bulgaria | ||
| 52 | Hospital Regional "Guillermo Grant Benavente" | Concepcion | Chile | ||
| 53 | Instituto Terapias Oncologicas Providencia | Santiago | Chile | ||
| 54 | Prosalud | Santiago | Chile | ||
| 55 | Someal SA | Santiago | Chile | ||
| 56 | Centro de Investigacion Clínica del Sur Freire | Temuco | Chile | ||
| 57 | Private Office | Temuco | Chile | ||
| 58 | Centro Integral de Reumatologia de Caribe | Barranquilla | Colombia | ||
| 59 | Fundación del caribe para la investigación medica Fundación BIOS | Barranquilla | Colombia | ||
| 60 | Centro Integral de Reumatologia e Inmunologia SAS | Bogota | Colombia | ||
| 61 | Cirei Sas | Bogota | Colombia | ||
| 62 | Idearg S.A.S. | Bogota | Colombia | ||
| 63 | Medicity S.A.S. | Bucaramanga | Colombia | ||
| 64 | Clinica de Arthritis Temprana S.A.S. | Cali | Colombia | ||
| 65 | Preventive Care SAS | Cundinamarca | Colombia | ||
| 66 | Hospital Pablo Tobon Uribe | Medellin | Colombia | ||
| 67 | Revmatologie S.R.O | Brno | Czechia | ||
| 68 | Ambulance Revmatologie a Interniho Lekarstvi | Kladno | Czechia | ||
| 69 | Revmatologicka ambulance | Praha-Nusle | Czechia | ||
| 70 | Medical Plus, s.r.o. | Uherske Hradiste | Czechia | ||
| 71 | PV-Medical | Zlin | Czechia | ||
| 72 | Hopitaux universitaires de Strasbourg | Strasbourg | France | ||
| 73 | Charite Mitte, Rheumatologie Neue Therapien | Berlin | Germany | ||
| 74 | Schlossparkklinik - Akad. Lehrkrankenhaus Charite | Berlin | Germany | ||
| 75 | Klinikum Goethe-Universität | Frankfurt | Germany | ||
| 76 | Schwerpunktpraxis fuer Rheumatologie | Hamburg | Germany | ||
| 77 | Rheumazentrum Ruhrgebiet | Herne | Germany | ||
| 78 | Centro Medico | Guatemala City | Guatemala | ||
| 79 | Clinica de Especialidades Medicas | Guatemala City | Guatemala | ||
| 80 | Clinica Medica Especializada en Reumatologia | Guatemala City | Guatemala | ||
| 81 | Clinica Medica | Guatemala City | Guatemala | ||
| 82 | Reuma S.A. | Guatemala City | Guatemala | ||
| 83 | Reuma-Centro | Guatemala | Guatemala | ||
| 84 | DRC | Balatonfured | Hungary | ||
| 85 | Budai Irgalmasrendi Korhaz | Budapest | Hungary | ||
| 86 | Qualiclinic Ltd | Budapest | Hungary | ||
| 87 | Revita Clinic | Budapest | Hungary | ||
| 88 | Markhot Ferenc Korhaz | Eger | Hungary | ||
| 89 | Bekes Megyei Pandy Kalman Korhaz, Reumatologiai Osztaly | Gyula | Hungary | ||
| 90 | Csolnoky Ferenc County Hospital | Veszprem | Hungary | ||
| 91 | Carmel Medical Center | Haifa | Israel | ||
| 92 | Rambam Medical Center | Haifa | Israel | ||
| 93 | Sheba Medical Center | Ramat Gan | Israel | ||
| 94 | M&M Centre Ltd. | Adazi | Latvia | ||
| 95 | Meda D | Daugavplis | Latvia | ||
| 96 | L. Atikes doktorats | Liepaja | Latvia | ||
| 97 | "Bruninieku" polyclinic | Riga | Latvia | ||
| 98 | Arija's Ancane's Family Doctor | Riga | Latvia | ||
| 99 | Centro de Estudios de Investigacion Basica y Clinica, SC | Guadalajara | Mexico | ||
| 100 | Arké Estudios Clínicos | Mexico | Mexico | ||
| 101 | Clinstile, S.A. de C.V. | Mexico | Mexico | ||
| 102 | Hospital General de México | Mexico | Mexico | ||
| 103 | Accelerium Clinical Research | Monterrey | Mexico | ||
| 104 | Hospital Universitario José E. González | Monterrey | Mexico | ||
| 105 | Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C. | San Luis Potosi | Mexico | ||
| 106 | IMSP Institutul de Cardiologie | Chisinau | Moldova, Republic of | ||
| 107 | North Shore hospital | Auckland | New Zealand | ||
| 108 | Waikato Hospital | Hamilton | New Zealand | ||
| 109 | Timaru Rheumatology Studies | Timaru | New Zealand | ||
| 110 | NZOZ Osteo-Medic s.c. | Bialystok | Poland | ||
| 111 | Silesiana Centrum Medyczne | Bytom | Poland | ||
| 112 | Medica Pro Familia Sp. z o.o. S.K.A. | Katowice | Poland | ||
| 113 | Centrum Medyczne Plejady | Krakow | Poland | ||
| 114 | Nowomed | Krakow | Poland | ||
| 115 | Nzoz "Dobry Lekarz" | Krakow | Poland | ||
| 116 | NZOZ Przychodnia Lekarska "Eskulap" | Skierniewice | Poland | ||
| 117 | NS ZOZ Medicus Bonus | Sroda Wielkopolska | Poland | ||
| 118 | Powiatowy Zakrad Opieki Zdrowotnej w Starachowicach | Starachowice | Poland | ||
| 119 | NZOZ Nasz Lekarz | Torun | Poland | ||
| 120 | AMED Medical Center | Warsaw | Poland | ||
| 121 | Wojewodzki Szpital Specjalistyczny we Wroclawiu | Wroclaw | Poland | ||
| 122 | I.M. Sechenov First Moscow State Medical University | Moscow | Russian Federation | ||
| 123 | Research Institute of Rheumatology RAMS | Moscow | Russian Federation | ||
| 124 | State University of Medicine and Dentistry | Moscow | Russian Federation | ||
| 125 | City Clinical Hospital 5 | Nizhniy Novgorod | Russian Federation | ||
| 126 | Ryazan State Medical University | Ryazan | Russian Federation | ||
| 127 | City Hospital # 26 | St Petersburg | Russian Federation | ||
| 128 | Vladimir Reg Clin Hosp | Vladimir | Russian Federation | ||
| 129 | Hospital Reina Sofa | Cordoba | Spain | ||
| 130 | Complejo Hospitalario Universitario A Coruña | Coruña | Spain | ||
| 131 | Hospital General Universitario de Elche | Elche | Spain | ||
| 132 | Hospital Universitario de Mostoles | Mostoles | Spain | ||
| 133 | Consorci Sanitari Parc Tauli | Sabadell | Spain | ||
| 134 | Hospital Infanta Luisa | Sevilla | Spain | ||
| 135 | City Hospital #5 | Donetsk | Ukraine | ||
| 136 | V. Gusak Institute of Urgent and Recovery Surgery | Donetsk | Ukraine | ||
| 137 | City Hospital #13 | Kharkiv | Ukraine | ||
| 138 | City Hospital #8 | Kharkiv | Ukraine | ||
| 139 | Government Institution | Kharkiv | Ukraine | ||
| 140 | Central Outpatient Hospital of Deanyanskyy Distric | Kiev | Ukraine | ||
| 141 | Central regional polyclinic of Pechersk District | Kyiv | Ukraine | ||
| 142 | Municipal Institution Lutsk City Clinical Hospital | Lutsk | Ukraine |
Sponsors and Collaborators
- Galapagos NV
Investigators
- Study Director: Galapagos Study Director, Galapagos NV
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Galapagos NV
ClinicalTrials.gov Identifier:
NCT01888874
Other Study ID Numbers:
- GLPG0634-CL-203 (DARWIN1)
- 2012-003635-31
First Posted:
Jun 28, 2013
Last Update Posted:
Nov 17, 2020
Last Verified:
Oct 1, 2020
Keywords provided by Galapagos NV
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at study sites in Europe, South America, North America, Australia, and New Zealand. The first participant was screened on 17 July 2013. The last study visit occurred on 14 May 2015. |
|---|---|
| Pre-assignment Detail | A total of 1255 participants were screened of which 599 participants were randomized into the study and only 594 participants were treated. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Period Title: Period 1 (Baseline up to Week 12) | |||||||
| STARTED | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| COMPLETED | 83 | 76 | 78 | 80 | 77 | 80 | 83 |
| NOT COMPLETED | 3 | 6 | 7 | 6 | 9 | 5 | 1 |
| Period Title: Period 1 (Baseline up to Week 12) | |||||||
| STARTED | 53 | 57 | 112 | 80 | 60 | 112 | 83 |
| COMPLETED | 50 | 55 | 104 | 78 | 57 | 109 | 80 |
| NOT COMPLETED | 3 | 2 | 8 | 2 | 3 | 3 | 3 |
Baseline Characteristics
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. | Total of all reporting groups |
| Overall Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 | 594 |
| Age (years) [Mean (Full Range) ] | ||||||||
| Mean (Full Range) [years] |
52
|
52.8
|
52.3
|
54.8
|
52.4
|
55.4
|
53.9
|
53.4
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
70
81.4%
|
69
84.1%
|
65
76.5%
|
74
86%
|
68
79.1%
|
65
76.5%
|
70
83.3%
|
481
81%
|
| Male |
16
18.6%
|
13
15.9%
|
20
23.5%
|
12
14%
|
18
20.9%
|
20
23.5%
|
14
16.7%
|
113
19%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||
| Hispanic or Latino |
37
43%
|
37
45.1%
|
33
38.8%
|
33
38.4%
|
37
43%
|
30
35.3%
|
38
45.2%
|
245
41.2%
|
| Not Hispanic or Latino |
49
57%
|
45
54.9%
|
52
61.2%
|
53
61.6%
|
49
57%
|
55
64.7%
|
46
54.8%
|
349
58.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
1
1.2%
|
0
0%
|
0
0%
|
1
1.2%
|
0
0%
|
2
0.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
1.2%
|
0
0%
|
0
0%
|
1
1.2%
|
0
0%
|
0
0%
|
1
1.2%
|
3
0.5%
|
| White |
59
68.6%
|
61
74.4%
|
62
72.9%
|
67
77.9%
|
63
73.3%
|
65
76.5%
|
66
78.6%
|
443
74.6%
|
| More than one race |
26
30.2%
|
21
25.6%
|
22
25.9%
|
18
20.9%
|
23
26.7%
|
19
22.4%
|
17
20.2%
|
146
24.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Rheumatoid Arthritis (RA) duration (years) [Mean (Full Range) ] | ||||||||
| Mean (Full Range) [years] |
8.21
|
7.21
|
7.67
|
8.51
|
8.88
|
7.79
|
9.74
|
8.29
|
| C-reactive protein (CRP) at Baseline (milligram per liter (mg/L)) [Mean (Full Range) ] | ||||||||
| Mean (Full Range) [milligram per liter (mg/L)] |
16.25
|
27.71
|
24.54
|
27.1
|
26.01
|
24.6
|
26.86
|
24.70
|
| Corrected tender joint count based on 68 joints (TJC68) at Baseline (joint count) [Mean (Full Range) ] | ||||||||
| Mean (Full Range) [joint count] |
24.984
|
24.907
|
25.319
|
28.843
|
25.427
|
27.158
|
25.946
|
26.091
|
| Corrected swollen joint count based on 66 joints (SJC66) at Baseline (joint count) [Mean (Full Range) ] | ||||||||
| Mean (Full Range) [joint count] |
16.13
|
17.023
|
16.31
|
17.355
|
15.663
|
17.534
|
16.356
|
16.622
|
Outcome Measures
| Title | Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12 |
|---|---|
| Description | The American College of Rheumatology (ACR) response is a measurement of improvement in multiple disease assessment criteria. The ACR20 response is defined as: 1) ≥ 20% improvement from baseline in SJC66, and 2) ≥ 20% improvement from baseline in tender TJC68, and 3) ≥ 20% improvement from baseline in at least 3 of the following 5 items: 1. Pain visual analog scale (VAS) (taken from the Health Assessment Questionnaire - Disability Index [HAQ-DI]), 2. Patient's Global Assessment of Disease Activity VAS, 3. Physician's Global Assessment of Disease Activity VAS, 4. Total HAQ-DI score, and 5. CRP. Non-responder imputation was used (ie, to impute a missing response, the participant was assumed to be a non-responder). |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all participants in the safety population who had post-randomization data for at least one efficacy parameter. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| Number [percentage of participants] |
44.2
51.4%
|
56.1
68.4%
|
63.5
74.7%
|
68.6
79.8%
|
57
66.3%
|
60
70.6%
|
78.6
93.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, GLPG0634 50 mg QD |
|---|---|---|
| Comments | Pairwise comparisons of each group vs. the placebo group using a logistic regression model with factors treatment group, geographical region, and prior use of biologics. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1236 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | P-value has been corrected for multiplicity according to Hommel's closed-testing method. | |
| Method of Estimation | Estimation Parameter | Difference in percentage rates |
| Estimated Value | 11.9 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to 26.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, GLPG0634 100 mg QD |
|---|---|---|
| Comments | Pairwise comparisons of each group vs. the placebo group using a logistic regression model with factors treatment group, geographical region, and prior use of biologics. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0435 |
| Comments | P-value has been corrected for multiplicity according to Hommel's closed-testing method. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage rates |
| Estimated Value | 19.3 | |
| Confidence Interval |
(2-Sided) 95% 4.7 to 34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, GLPG0634 200 mg QD |
|---|---|---|
| Comments | Pairwise comparisons of each group vs. the placebo group using a logistic regression model with factors treatment group, geographical region, and prior use of biologics. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0068 |
| Comments | P-value has been corrected for multiplicity according to Hommel's closed-testing method. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage rates |
| Estimated Value | 24.4 | |
| Confidence Interval |
(2-Sided) 95% 10.1 to 38.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, GLPG0634 25 mg BID |
|---|---|---|
| Comments | Pairwise comparisons of each group vs. the placebo group using a logistic regression model with factors treatment group, geographical region, and prior use of biologics. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1236 |
| Comments | P-value has been corrected for multiplicity according to Hommel's closed-testing method. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage rates |
| Estimated Value | 12.8 | |
| Confidence Interval |
(2-Sided) 95% -2 to 27.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, GLPG0634 50 mg BID |
|---|---|---|
| Comments | Pairwise comparisons of each group vs. the placebo group using a logistic regression model with factors treatment group, geographical region, and prior use of biologics. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1056 |
| Comments | P-value has been corrected for multiplicity according to Hommel's closed-testing method. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage rates |
| Estimated Value | 15.8 | |
| Confidence Interval |
(2-Sided) 95% 1 to 30.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, GLPG0634 100 mg BID |
|---|---|---|
| Comments | Pairwise comparisons of each group vs. the placebo group using a logistic regression model with factors treatment group, geographical region, and prior use of biologics. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | P-value has been corrected for multiplicity according to Hommel's closed-testing method. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage rates |
| Estimated Value | 34.4 | |
| Confidence Interval |
(2-Sided) 95% 20.7 to 48.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving an ACR20 Response at Week 24 |
|---|---|
| Description | ACR20 response was defined as: 1) ≥ 20% improvement from baseline in SJC66, and 2) ≥ 20% improvement from baseline in TJC68, and 3) ≥ 20% improvement from baseline in at least 3 of the following 5 items: 1. Pain VAS (taken from the HAQ-DI), 2. Patient's Global Assessment of Disease Activity VAS, 3. Physician's Global Assessment of Disease Activity VAS, 4. Total HAQ-DI score, and 5. CRP. Non-responder imputation was used. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Participants who switched treatment at Week 12 were handled as if they discontinued at Week 12. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| Number [percentage of participants] |
41.9
48.7%
|
54.9
67%
|
61.2
72%
|
73.3
85.2%
|
55.8
64.9%
|
60
70.6%
|
79.8
95%
|
| Title | Percentage of Participants Achieving an ACR50 Response at Weeks 1, 2, 4, 8, 12, and 24 |
|---|---|
| Description | ACR50 response was defined as: 1) ≥ 50% improvement from baseline in SJC66, and 2) ≥ 50% improvement from baseline in TJC68, and 3) ≥ 50% improvement from baseline in at least 3 of the following 5 items: 1. Pain VAS (taken from the HAQ-DI) 2. Patient's Global Assessment of Disease Activity VAS 3. Physician's Global Assessment of Disease Activity VAS 4. Total HAQ-DI score 5. CRP. Non-responder imputation was used. |
| Time Frame | Weeks 1, 2, 4, 8, 12, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Participants who switched treatment at Week 12 were handled as if they discontinued at Week 12. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| Week 1 |
1.2
1.4%
|
2.4
2.9%
|
4.7
5.5%
|
4.7
5.5%
|
3.5
4.1%
|
7.1
8.4%
|
7.1
8.5%
|
| Week 2 |
5.8
6.7%
|
7.3
8.9%
|
20
23.5%
|
10.5
12.2%
|
7
8.1%
|
11.8
13.9%
|
21.4
25.5%
|
| Week 4 |
7
8.1%
|
13.4
16.3%
|
32.9
38.7%
|
17.4
20.2%
|
15.1
17.6%
|
18.8
22.1%
|
34.5
41.1%
|
| Week 8 |
12.8
14.9%
|
26.8
32.7%
|
35.3
41.5%
|
33.7
39.2%
|
25.6
29.8%
|
34.1
40.1%
|
45.2
53.8%
|
| Week 12 |
15.1
17.6%
|
32.9
40.1%
|
37.6
44.2%
|
43
50%
|
27.9
32.4%
|
34.1
40.1%
|
54.8
65.2%
|
| Week 24 |
16.3
19%
|
35.4
43.2%
|
47.1
55.4%
|
50
58.1%
|
34.9
40.6%
|
35.3
41.5%
|
54.8
65.2%
|
| Title | Percentage of Participants Achieving an ACR70 Response at Weeks 1, 2, 4, 8, 12, and 24 |
|---|---|
| Description | ACR70 response: 1) ≥ 70% improvement from baseline in SJC66, and 2) ≥ 70% improvement from baseline in TJC68, and 3) ≥ 70% improvement from baseline in at least 3 of the following 5 items: 1. Pain VAS (taken from the HAQ-DI), 2. Patient's Global Assessment of Disease Activity VAS, 3. Physician's Global Assessment of Disease Activity VAS, 4. Total HAQ-DI score, and 5. CRP. Non-responder imputation was used. |
| Time Frame | Weeks 1, 2, 4, 8, 12, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Participants who switched treatment at Week 12 were handled as if they discontinued at Week 12. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| Week 1 |
1.2
1.4%
|
0
0%
|
0
0%
|
1.2
1.4%
|
1.2
1.4%
|
2.4
2.8%
|
4.8
5.7%
|
| Week 2 |
1.2
1.4%
|
2.4
2.9%
|
7.1
8.4%
|
5.8
6.7%
|
2.3
2.7%
|
5.9
6.9%
|
3.6
4.3%
|
| Week 4 |
3.5
4.1%
|
7.3
8.9%
|
14.1
16.6%
|
4.7
5.5%
|
5.8
6.7%
|
9.4
11.1%
|
10.7
12.7%
|
| Week 8 |
7
8.1%
|
11
13.4%
|
23.5
27.6%
|
18.6
21.6%
|
9.3
10.8%
|
14.1
16.6%
|
27.4
32.6%
|
| Week 12 |
8.1
9.4%
|
15.9
19.4%
|
21.2
24.9%
|
24.4
28.4%
|
14
16.3%
|
18.8
22.1%
|
31
36.9%
|
| Week 24 |
9.3
10.8%
|
22
26.8%
|
32.9
38.7%
|
29.1
33.8%
|
20.9
24.3%
|
23.5
27.6%
|
39.3
46.8%
|
| Title | ACR N% Improvement (ACR-N) Response at Weeks 1, 2, 4, 8, 12, and 24 |
|---|---|
| Description | The ACR-N is the smallest percentage improvement in swollen and tender joints and the median of the remaining 5 core parameters, and is expected to be more sensitive to change than the ACR20, ACR50 or ACR70. It is a number varying between 0 and 100, with higher numbers indicating less severity of symptoms. Last observation carried forward (LOCF) algorithm was used (ie, to impute a missing value, the last preceding nonmissing value was used). |
| Time Frame | Weeks 1, 2, 4, 8, 12, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population with available data were analyzed. Participants who switched treatment at Week 12 were handled as if they discontinued at Week 12. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 84 | 82 | 80 | 86 | 83 | 85 | 82 |
| Week 1 |
9.27
(1.519)
|
10.31
(1.578)
|
14.69
(2.04)
|
14.25
(1.822)
|
9.01
(1.603)
|
11.36
(1.939)
|
17.63
(2.206)
|
| Week 2 |
13.85
(1.949)
|
16.36
(2.125)
|
25.2
(1.986)
|
22.61
(2.517)
|
15.2
(2.063)
|
20.01
(2.47)
|
27.77
(2.606)
|
| Week 4 |
16.93
(2.332)
|
21.08
(2.598)
|
31.32
(3.354)
|
27.45
(2.573)
|
23.17
(2.668)
|
26.37
(2.961)
|
35.69
(2.861)
|
| Week 8 |
21.6
(2.644)
|
30.16
(3.015)
|
38.24
(3.484)
|
37.88
(3.097)
|
31.2
(2.845)
|
33.4
(3.15)
|
45.36
(3.246)
|
| Week 12 |
23.09
(2.911)
|
34.03
(3.335)
|
39.87
(3.449)
|
42.1
(3.277)
|
34.12
(3.144)
|
35.86
(3.29)
|
51.17
(3.379)
|
| Week 24 |
22.06
(2.846)
|
37.13
(3.582)
|
50.86
(3.645)
|
50.4
(3.291)
|
38.56
(3.384)
|
40.5
(3.299)
|
58.69
(3.204)
|
| Title | 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 |
|---|---|
| Description | DAS28 (CRP) was categorized into EULAR response categories (none, moderate, good) as follows: None = Actual DAS28 (CRP) ≤ 3.2, > 3.2 to ≤ 5.1, or > 5.1 AND Improvement in DAS28 (CRP) from baseline ≤ 6.0 or > 0.6 to ≤ 1.2; Moderate = Actual DAS28 (CRP) ≤ 3.2 AND Improvement in DAS28 (CRP) from baseline > 0.6 to ≤ 1.2, Actual DAS28 (CRP) > 3.2 to ≤ 5.1 or > 5.1 AND Improvement in DAS28 (CRP) from baseline > 1.2, or Actual DAS28 (CRP) > 3.2 to ≤ 5.1 AND Improvement in DAS28 (CRP) from baseline > 0.6 to ≤ 1.2; Good = Actual DAS28 (CRP) ≤ 3.2 AND Improvement in DAS28 (CRP) from baseline > 1.2. LOCF algorithm was used. |
| Time Frame | Weeks 1, 2, 4, 8, 12, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Participants who switched treatment at Week 12 were handled as if they discontinued at Week 12. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| Week 1: None |
73
84.9%
|
61
74.4%
|
58
68.2%
|
42
48.8%
|
63
73.3%
|
64
75.3%
|
40
47.6%
|
| Week 1: Moderate |
21
24.4%
|
38
46.3%
|
35
41.2%
|
55
64%
|
34
39.5%
|
32
37.6%
|
49
58.3%
|
| Week 1: Good |
6
7%
|
1
1.2%
|
7
8.2%
|
3
3.5%
|
3
3.5%
|
5
5.9%
|
11
13.1%
|
| Week 2: None |
58
67.4%
|
49
59.8%
|
39
45.9%
|
31
36%
|
51
59.3%
|
44
51.8%
|
20
23.8%
|
| Week 2: Moderate |
33
38.4%
|
45
54.9%
|
42
49.4%
|
53
61.6%
|
43
50%
|
46
54.1%
|
62
73.8%
|
| Week 2: Good |
9
10.5%
|
6
7.3%
|
19
22.4%
|
15
17.4%
|
6
7%
|
11
12.9%
|
18
21.4%
|
| Week 4: None |
56
65.1%
|
44
53.7%
|
29
34.1%
|
16
18.6%
|
37
43%
|
35
41.2%
|
15
17.9%
|
| Week 4: Moderate |
34
39.5%
|
46
56.1%
|
40
47.1%
|
65
75.6%
|
44
51.2%
|
42
49.4%
|
61
72.6%
|
| Week 4: Good |
10
11.6%
|
10
12.2%
|
31
36.5%
|
19
22.1%
|
19
22.1%
|
22
25.9%
|
24
28.6%
|
| Week 8: None |
44
51.2%
|
34
41.5%
|
20
23.5%
|
15
17.4%
|
24
27.9%
|
24
28.2%
|
8
9.5%
|
| Week 8: Moderate |
43
50%
|
45
54.9%
|
52
61.2%
|
49
57%
|
51
59.3%
|
49
57.6%
|
46
54.8%
|
| Week 8: Good |
13
15.1%
|
21
25.6%
|
28
32.9%
|
36
41.9%
|
24
27.9%
|
27
31.8%
|
45
53.6%
|
| Week 12: None |
41
47.7%
|
33
40.2%
|
18
21.2%
|
8
9.3%
|
28
32.6%
|
15
17.6%
|
7
8.3%
|
| Week 12: Moderate |
45
52.3%
|
44
53.7%
|
48
56.5%
|
55
64%
|
44
51.2%
|
56
65.9%
|
43
51.2%
|
| Week 12: Good |
14
16.3%
|
23
28%
|
34
40%
|
37
43%
|
28
32.6%
|
28
32.9%
|
50
59.5%
|
| Week 24: None |
48
55.8%
|
33
40.2%
|
12
14.1%
|
10
11.6%
|
23
26.7%
|
14
16.5%
|
5
6%
|
| Week 24: Moderate |
34
39.5%
|
35
42.7%
|
38
44.7%
|
38
44.2%
|
37
43%
|
49
57.6%
|
31
36.9%
|
| Week 24: Good |
19
22.1%
|
32
39%
|
51
60%
|
51
59.3%
|
40
46.5%
|
36
42.4%
|
64
76.2%
|
| Title | Percentage of Participants Achieving ACR/EULAR Remission at Weeks 2, 4, 8, 12, and 24 |
|---|---|
| Description | A participant's disease activity status can be defined as being in remission when scores on the TJC28, SJC28, CRP (actual value in mg/dL) and Patient Global Assessment of Disease Activity (cm) are all ≤ 1. Non-responder imputation was used. |
| Time Frame | Weeks 2, 4, 8, 12, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Participants who switched treatment at Week 12 were handled as if they discontinued at Week 12. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| Week 2 |
0
0%
|
0
0%
|
3.5
4.1%
|
0
0%
|
0
0%
|
0
0%
|
1.2
1.4%
|
| Week 4 |
1.2
1.4%
|
1.2
1.5%
|
1.2
1.4%
|
2.3
2.7%
|
0
0%
|
0
0%
|
2.4
2.9%
|
| Week 8 |
1.2
1.4%
|
3.7
4.5%
|
3.5
4.1%
|
3.5
4.1%
|
1.2
1.4%
|
1.2
1.4%
|
3.6
4.3%
|
| Week 12 |
3.5
4.1%
|
3.7
4.5%
|
3.5
4.1%
|
5.8
6.7%
|
4.7
5.5%
|
4.7
5.5%
|
9.5
11.3%
|
| Week 24 |
1.2
1.4%
|
11
13.4%
|
8.2
9.6%
|
11.6
13.5%
|
5.8
6.7%
|
3.5
4.1%
|
19
22.6%
|
| Title | Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 1, 2, 4, 8, 12, and 24 |
|---|---|
| Description | The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, Patient Global Assessment of Disease Activity (in cm), Physician's Global Assessment of Disease Activity (in cm), and CRP (mg/dL). The SDAI was categorized as follows: • High disease activity: SDAI > 26 • Moderate disease activity: 11 to 26 • Low disease activity: 3.3 to 11 • Remission: ≤ 3.3. LOCF algorithm was used. The SDAI total score ranges from 0 to approximately 86. |
| Time Frame | Baseline and Weeks 1, 2, 4, 8, 12, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population with available data were analyzed. Participants who switched treatment at Week 12 were handled as if they discontinued at Week 12. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| Baseline |
43.756
(1.2717)
|
43.77
(1.3499)
|
45.42
(1.3909)
|
45.611
(1.3362)
|
43.951
(1.3224)
|
44.794
(1.4043)
|
44.542
(1.3097)
|
| Change at Week 1 |
-8.3
(1.25)
|
-8
(1.14)
|
-12.2
(1.45)
|
-12.8
(1.29)
|
-8.2
(1.17)
|
-10
(1.22)
|
-14.5
(1.31)
|
| Change at Week 2 |
-11.4
(1.45)
|
-12.5
(1.46)
|
-18.6
(1.64)
|
-16.4
(1.35)
|
-13.4
(1.29)
|
-15.1
(1.43)
|
-20.3
(1.35)
|
| Change at Week 4 |
-13.1
(1.47)
|
-16.3
(1.64)
|
-22.7
(1.78)
|
-22.2
(1.28)
|
-17.8
(1.44)
|
-19.3
(1.74)
|
-24.9
(1.54)
|
| Change at Week 8 |
-16.3
(1.64)
|
-20.1
(1.86)
|
-24.6
(1.57)
|
-25.9
(1.57)
|
-22.2
(1.68)
|
-23.2
(1.8)
|
-29.2
(1.58)
|
| Change at Week 12 |
-16.3
(1.84)
|
-21
(1.84)
|
-25.2
(1.69)
|
-27.2
(1.55)
|
-22.3
(1.71)
|
-24.5
(1.87)
|
-30.6
(1.57)
|
| Change at Week 24 |
-15.8
(2)
|
-22.8
(2.07)
|
-30.1
(1.66)
|
-31
(1.66)
|
-24.9
(1.85)
|
-27.9
(2)
|
-34.4
(1.47)
|
| Title | Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 1, 2, 4, 8, 12, and 24 |
|---|---|
| Description | The CDAI is the SDAI modified to exclude CRP and is the sum of the 4 outcome parameters: TJC28, SJC28, Patient Global Assessment of Disease Activity (in cm), and Physician's Global Assessment of Disease Activity (in cm). The CDAI was be categorized as follows: • High disease activity: > 22 • Moderate disease activity: 10 to 22 • Mild disease activity: 2.8 to 10 • Remission: ≤ 2.8. LOCF algorithm was used. The CDAI total score ranges from 0 to approximately 76. |
| Time Frame | Baseline and Weeks 1, 2, 4, 8, 12, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population with available data were analyzed. Participants who switched treatment at Week 12 were handled as if they discontinued at Week 12. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| Baseline |
42.131
(1.236)
|
40.999
(1.2104)
|
42.966
(1.3014)
|
42.901
(1.2844)
|
41.347
(1.2442)
|
42.333
(1.3186)
|
41.856
(1.2462)
|
| Change at Week 1 |
-8.5
(1.23)
|
-7.2
(1.09)
|
-11.1
(1.38)
|
-11.1
(1.22)
|
-7.3
(1.14)
|
-9
(1.15)
|
-12.8
(1.27)
|
| Change at Week 2 |
-11.6
(1.43)
|
-11.7
(1.39)
|
-17.3
(1.58)
|
-14.6
(1.29)
|
-12.4
(1.26)
|
-14
(1.38)
|
-18.4
(1.31)
|
| Change at Week 4 |
-13.3
(1.42)
|
-15.2
(1.54)
|
-21.4
(1.71)
|
-20.4
(1.24)
|
-17.1
(1.35)
|
-18
(1.71)
|
-22.8
(1.51)
|
| Change at Week 8 |
-16.4
(1.58)
|
-18.9
(1.78)
|
-23.4
(1.52)
|
-24.2
(1.15)
|
-21.1
(1.67)
|
-21.9
(1.75)
|
-27.1
(1.53)
|
| Change at Week 12 |
-16.6
(1.84)
|
-19.7
(1.77)
|
-23.8
(1.66)
|
-25.5
(1.5)
|
-21.3
(1.65)
|
-23.2
(1.81)
|
-28.5
(1.49)
|
| Change at Week 24 |
-16
(1.95)
|
-21.3
(1.97)
|
-28.6
(1.63)
|
-29.4
(1.5)
|
-23.8
(1.75)
|
-26.7
(1.9)
|
-32.4
(1.39)
|
| Title | Change From Baseline in Quality of Life Using the Functional Assessment of Chronic Illness Therapy (FACIT) at Weeks 4, 12, and 24 |
|---|---|
| Description | FACIT-Fatigue scale is a 13-item questionnaire, each scored on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated that are scored reversely), the greater the fatigue. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score), with a higher score indicating a better quality of life. LOCF algorithm was used. |
| Time Frame | Baseline and Weeks 4, 12, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population with available data were analyzed. Participants who switched treatment at Week 12 were handled as if they discontinued at Week 12. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| Baseline |
26.2
(1.09)
|
26.2
(1.1)
|
26.6
(1.06)
|
25.2
(1.25)
|
28.1
(1.18)
|
26.2
(1.04)
|
25.6
(1.25)
|
| Change at Week 4 |
4.9
(1.06)
|
4.4
(1.11)
|
9.1
(1.14)
|
8.5
(1.23)
|
4.5
(1.06)
|
6.6
(0.88)
|
9.9
(0.97)
|
| Change at Week 12 |
5.6
(1.06)
|
7.6
(1.26)
|
9.5
(1.21)
|
11.4
(1.37)
|
6.9
(1.12)
|
8.4
(1.08)
|
11.3
(1.25)
|
| Change at Week 24 |
6
(1.04)
|
7.9
(1.21)
|
11.1
(1.2)
|
11.6
(1.33)
|
7.7
(1.17)
|
9
(1.04)
|
12.8
(1.36)
|
| Title | Change From Baseline in Quality of Life Using the Short Form-36 (SF-36) Scores at Weeks 4, 12, and 24 |
|---|---|
| Description | The SF-36 is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores were computed based on weighted combinations of the 8 domain scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). LOCF algorithm was used. |
| Time Frame | Baseline and Weeks 4, 12, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population with available data were analyzed. Participants who switched treatment at Week 12 were handled as if they discontinued at Week 12. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. |
| Measure Participants | 86 | 82 | 85 | 86 | 86 | 85 | 84 |
| PCS at Baseline |
32.999
(0.7121)
|
32.691
(0.7474)
|
31.636
(0.7926)
|
31.625
(0.6355)
|
31.364
(0.6858)
|
31.332
(0.726)
|
32.249
(0.7844)
|
| PCS Change at Week 4 |
3
(0.65)
|
4.1
(0.88)
|
6.1
(0.98)
|
6.4
(0.87)
|
5
(0.69)
|
4.2
(0.8)
|
7.2
(0.77)
|
| PCS Change at Week 12 |
3.2
(0.74)
|
6.7
(1)
|
8.4
(0.93)
|
8.9
(0.9)
|
7.5
(0.92)
|
7.1
(0.96)
|
10.5
(0.98)
|
| PCS Change at Week 24 |
2.8
(0.75)
|
7.3
(1.02)
|
9.9
(1.09)
|
9.7
(0.99)
|
7.8
(0.85)
|
7.9
(0.91)
|
11.6
(1.1)
|
| MCS at Baseline |
42.849
(1.0861)
|
42.199
(1.2581)
|
43.953
(1.1118)
|
41.362
(1.1427)
|
45.527
(1.288)
|
44.748
(1.228)
|
42.059
(1.2898)
|
| MCS at Week 4 |
3
(0.92)
|
3.4
(0.91)
|
4.9
(0.85)
|
5.4
(0.98)
|
2.4
(0.78)
|
2.7
(0.84)
|
5.6
(0.92)
|
| MCS at Week 12 |
4.3
(1.05)
|
4.4
(1.11)
|
5.1
(0.96)
|
8.1
(1.17)
|
3.5
(0.97)
|
3.1
(1.02)
|
6.2
(0.98)
|
| MCS at Week 24 |
4.7
(0.96)
|
4.3
(1.04)
|
6.7
(0.91)
|
7.2
(1.12)
|
3.8
(0.96)
|
3.5
(1.01)
|
7.1
(1.21)
|
Adverse Events
| Time Frame | Baseline through end of study drug treatment (average exposure: 160.7 days) plus 10 days | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Nonresponders from Placebo (15 participants), 50 mg QD (19 participants) moved to 100 mg QD group and nonresponders from Placebo (15 participants) and 25 mg BID (17 participants) moved to 50 mg BID group from Week 13 to Week 24. | |||||||||||||
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID | |||||||
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, 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 mg QD or 50 mg BID during Weeks 13 to 24. | 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. | Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24. | Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24. | 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. | Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24. | Participants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24. | |||||||
All Cause Mortality |
||||||||||||||
| Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/86 (0%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 1/84 (1.2%) | |||||||
Serious Adverse Events |
||||||||||||||
| Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/86 (4.7%) | 0/82 (0%) | 4/119 (3.4%) | 2/86 (2.3%) | 2/86 (2.3%) | 0/117 (0%) | 3/84 (3.6%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 0/86 (0%) | 0/82 (0%) | 1/119 (0.8%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Pancytopenia | 0/86 (0%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 1/84 (1.2%) | |||||||
| Cardiac disorders | ||||||||||||||
| Pericardial effusion | 1/86 (1.2%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Angina unstable | 0/86 (0%) | 0/82 (0%) | 1/119 (0.8%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Acute myocardial infarction | 0/86 (0%) | 0/82 (0%) | 1/119 (0.8%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Ear and labyrinth disorders | ||||||||||||||
| Vertigo | 0/86 (0%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 1/84 (1.2%) | |||||||
| General disorders | ||||||||||||||
| Inflammation | 1/86 (1.2%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Appendicitis | 1/86 (1.2%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Pneumonia | 0/86 (0%) | 0/82 (0%) | 1/119 (0.8%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 1/84 (1.2%) | |||||||
| Diabetic gangrene | 0/86 (0%) | 0/82 (0%) | 1/119 (0.8%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Subcutaneous abscess | 0/86 (0%) | 0/82 (0%) | 1/119 (0.8%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Erysipelas | 0/86 (0%) | 0/82 (0%) | 0/119 (0%) | 1/86 (1.2%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Intervertebral discitis | 0/86 (0%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 1/84 (1.2%) | |||||||
| Septic shock | 0/86 (0%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 1/84 (1.2%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Lower limb fracture | 0/86 (0%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 1/84 (1.2%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Dehydration | 1/86 (1.2%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Muscle twitching | 1/86 (1.2%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Ischaemic cerebral infarction | 0/86 (0%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 1/86 (1.2%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||
| Abortion spontaneous | 0/86 (0%) | 0/82 (0%) | 0/119 (0%) | 1/86 (1.2%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Abortion spontaneous complete | 0/86 (0%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 1/86 (1.2%) | 0/117 (0%) | 0/84 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Hyperventilation | 1/86 (1.2%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 0/117 (0%) | 0/84 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | GLPG0634 25 mg BID | GLPG0634 50 mg BID | GLPG0634 100 mg BID | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/86 (12.8%) | 23/82 (28%) | 13/119 (10.9%) | 21/86 (24.4%) | 23/86 (26.7%) | 22/117 (18.8%) | 15/84 (17.9%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Nausea | 3/86 (3.5%) | 7/82 (8.5%) | 0/119 (0%) | 3/86 (3.5%) | 3/86 (3.5%) | 3/117 (2.6%) | 1/84 (1.2%) | |||||||
| Vomiting | 1/86 (1.2%) | 0/82 (0%) | 0/119 (0%) | 0/86 (0%) | 0/86 (0%) | 6/117 (5.1%) | 2/84 (2.4%) | |||||||
| Infections and infestations | ||||||||||||||
| Gastroenteritis | 0/86 (0%) | 1/82 (1.2%) | 1/119 (0.8%) | 2/86 (2.3%) | 5/86 (5.8%) | 2/117 (1.7%) | 1/84 (1.2%) | |||||||
| Nasopharyngitis | 4/86 (4.7%) | 8/82 (9.8%) | 3/119 (2.5%) | 3/86 (3.5%) | 4/86 (4.7%) | 2/117 (1.7%) | 4/84 (4.8%) | |||||||
| Upper respiratory tract infection | 1/86 (1.2%) | 2/82 (2.4%) | 2/119 (1.7%) | 4/86 (4.7%) | 4/86 (4.7%) | 6/117 (5.1%) | 2/84 (2.4%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Hypercholesterolaemia | 0/86 (0%) | 2/82 (2.4%) | 0/119 (0%) | 5/86 (5.8%) | 2/86 (2.3%) | 1/117 (0.9%) | 4/84 (4.8%) | |||||||
| Nervous system disorders | ||||||||||||||
| Headache | 4/86 (4.7%) | 1/82 (1.2%) | 1/119 (0.8%) | 6/86 (7%) | 6/86 (7%) | 3/117 (2.6%) | 2/84 (2.4%) | |||||||
| Vascular disorders | ||||||||||||||
| Hypertension | 2/86 (2.3%) | 3/82 (3.7%) | 6/119 (5%) | 4/86 (4.7%) | 3/86 (3.5%) | 4/117 (3.4%) | 1/84 (1.2%) | |||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The sponsor must review and approve any results of the study or abstracts for professional meetings prepared by the investigator(s). Published data must not compromise the objectives of the study. Data from individual study centers in multicenter studies must not be published separately.
Results Point of Contact
| Name/Title | Clinical Trial Information Desk |
|---|---|
| Organization | Galapagos N.V. |
| Phone | +32 (0)15 342 900 |
| rd@glpg.com |
Responsible Party:
Galapagos NV
ClinicalTrials.gov Identifier:
NCT01888874
Other Study ID Numbers:
- GLPG0634-CL-203 (DARWIN1)
- 2012-003635-31
First Posted:
Jun 28, 2013
Last Update Posted:
Nov 17, 2020
Last Verified:
Oct 1, 2020