Dose-finding Study of GLPG0634 as Monotherapy in Active Rheumatoid Arthritis (RA) Participants (DARWIN2)
Study Details
Study Description
Brief Summary
-
Participants suffering from active rheumatoid arthritis who had an inadequate response to methotrexate were evaluated for improvement of disease activity (efficacy) when taking GLPG0634 as monotherapy (3 different doses - 50 milligram (mg), 100 mg and 200 mg once daily) 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 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, all participants on placebo and the participants on the 50 mg dose who had not achieved 20% improvement in swollen joint count (SJC66) and tender joint count (TJC68) were assigned (automatically via interactive web response system (IWRS)) to 100 mg once daily (QD) in a blinded fashion and continued treatment until Week 24.
-
Participants in the other groups maintained their randomized treatment until Week 24.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Participants received GLPG0634 matching placebo capsules, orally, once daily (QD) during Weeks 1 to 12 and GLPG0634 100 milligram (mg) QD 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.
|
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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24.
- 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24.
- 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). All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24.
- 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24.
- Percentage of Participants Achieving ACR/EULAR Remission at Weeks 2, 4, 8, 12, and 24 [Weeks 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24.
- 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24.
- 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24.
- 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24.
- 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Artho Care, Arthritis Care & Research P.C. | Gilbert | Arizona | United States | |
| 2 | Arizona Arthritis & Rheumatology Research PLLC | Mesa | Arizona | United States | |
| 3 | Arizona Arthritis Rheum Res | Phoenix | Arizona | United States | |
| 4 | Little Rock Diagnostic Clinic | Little Rock | Arkansas | United States | |
| 5 | C.V. Mehta MD Medical Corp. | Hemet | California | United States | |
| 6 | Center for Innovative Therapy Division of Rheumatology, UCSD | La Jolla | California | United States | |
| 7 | Desert Medical Advances | Palm Desert | California | United States | |
| 8 | Infosphere Clinical Research, Inc. | West Hills | California | United States | |
| 9 | Lovelace Scientific Resources | Venice | Florida | United States | |
| 10 | Arthritis Center of North GA | Gainesville | Georgia | United States | |
| 11 | The Arthritis Center | Springfield | Illinois | United States | |
| 12 | Klein and Associates MD | Hagerstown | Maryland | United States | |
| 13 | Private practice | Lansing | Michigan | United States | |
| 14 | Arthritis Center of Reno | Reno | Nevada | United States | |
| 15 | New Jersey Physicians, LLC | Clifton | New Jersey | United States | |
| 16 | Health research of Oklahoma | Oklahoma City | Oklahoma | United States | |
| 17 | Altoona Center Clin Research | Duncansville | Pennsylvania | United States | |
| 18 | Low Country Rheumatology, PA | Charleston | South Carolina | United States | |
| 19 | Arthritis Clinic | Jackson | Tennessee | United States | |
| 20 | Austin Rheumatology Research PA | Austin | Texas | United States | |
| 21 | Pioneer Research Solutions Inc | Houston | Texas | United States | |
| 22 | Centro de Investigaciones Medicas Lanus | Lanus | Argentina | ||
| 23 | Instituto Centralizado de Asistencia e investigacion Clinica Integral | Rosario | Argentina | ||
| 24 | Centro Médico Privado de Reumatología | Tucuman | Argentina | ||
| 25 | Royal Prince Alfred Hospital | Camperdown | Australia | ||
| 26 | Princess Alexandra Hospital | Woolloongabba | Australia | ||
| 27 | Rheumazentrum Favoriten | Wien | Austria | ||
| 28 | "Multiprofile Hospital for Active Treatment - Kaspela" LTD | Plovdiv | Bulgaria | ||
| 29 | Clinic of Rheumatology MHAT | Sofia | Bulgaria | ||
| 30 | Hospital Regional "Guillermo Grant Benavente" | Concepcion | Chile | ||
| 31 | Private Office | Temuco | Chile | ||
| 32 | Fundación del Caribe para la Investigación Biomédica BIOS | Barranquilla | Colombia | ||
| 33 | Centro Integral de Reumatologia SAS | Bogota | Colombia | ||
| 34 | Cirei Sas | Bogota | Colombia | ||
| 35 | Idearg S.A.S. | Bogota | Colombia | ||
| 36 | Medicity S.A.S. | Bucaramanga | Colombia | ||
| 37 | Preventive Care Ltda | Chia | Colombia | ||
| 38 | Schlossparkklinik - Akad. Lehrkrankenhaus Charite | Berlin | Germany | ||
| 39 | Schwerpunktpraxis fuer Rheumatologie | Hamburg | Germany | ||
| 40 | Clinica Médica Especializada en Medicina Interna | Guatemala City | Guatemala | ||
| 41 | Reuma S.A. | Guatemala City | Guatemala | ||
| 42 | Reuma-Centro | Guatemala City | Guatemala | ||
| 43 | DRC | Balatonfüred | Hungary | ||
| 44 | Qualiclinic Ltd | Budapest | Hungary | ||
| 45 | Revita Clinic | Budapest | Hungary | ||
| 46 | Csolnoky Ferenc County Hospital | Veszprem | Hungary | ||
| 47 | L. Atikes doktorats | Liepaja | Latvia | ||
| 48 | "Bruninieku" Polyclinic | Riga | Latvia | ||
| 49 | Arké Estudios Clínicos S.A. de C.V. | Mexico | Mexico | ||
| 50 | Centro Medico Dalinde | Mexico | Mexico | ||
| 51 | Clinstile, S.A. de C.V. | Mexico | Mexico | ||
| 52 | Mexico Centre for Clinical Research | Mexico | Mexico | ||
| 53 | Hospital Universitario | Monterrey | Mexico | ||
| 54 | Hospital de Especialidades | Oaxaca | Mexico | ||
| 55 | IMSP Institutul de Cardiologie | Chisinau | Moldova, Republic of | ||
| 56 | North Shore hospital | Auckland | New Zealand | ||
| 57 | Timaru Rheumatology Studies | Timaru | New Zealand | ||
| 58 | Silesiana Centrum Medyczne | Bytom | Poland | ||
| 59 | Centrum Kliniczno | Elblag | Poland | ||
| 60 | Medica Pro Familia Sp. z o.o. S.K.A. | Katowice | Poland | ||
| 61 | Nowomed | Krakow | Poland | ||
| 62 | Nzoz "Dobry Lekarz" | Krakow | Poland | ||
| 63 | NZOZ Przychodnia Lekarska "Eskulap" | Skierniewice | Poland | ||
| 64 | NZOZ Medicus Bonus | Sroda Wielkopolska | Poland | ||
| 65 | AMED Medical Center | Warsaw | Poland | ||
| 66 | Ars Rheumatica Sp. Z.o.o. | Warszawa | Poland | ||
| 67 | Wojewodzki Szpital Specjalistyczny we Wroclawiu | Wroclaw | Poland | ||
| 68 | Ianuli Med Consult SRL | Bucharest | Romania | ||
| 69 | Sana Medical Center | Bucuresti | Romania | ||
| 70 | Spitalul Clinic Sfanta Maria | Bucuresti | Romania | ||
| 71 | Emergency County Hospital | Galati | Romania | ||
| 72 | Orenburg State Medical Academy | Orenburg | Russian Federation | ||
| 73 | GUZ "Regional Clinical Hospital" | Saratov | Russian Federation | ||
| 74 | Vladimir Reg Clin Hosp | Vladimir | Russian Federation | ||
| 75 | Hospital General Elche | Elche | Spain | ||
| 76 | Consorci Sanitari Parc Tauli | Sabadell | Spain | ||
| 77 | CICEC S.L.P Hospital Ntra.Sra.de la Esperanza | Santiago De Compostella | Spain | ||
| 78 | V. Gusak Institute of Urgent and Recovery Surgery | Donetsk | Ukraine | ||
| 79 | City Hospital #8 | Kharkiv | Ukraine | ||
| 80 | Municipal Hospital | Kherson | Ukraine | ||
| 81 | Central Outpatient Hospital of Deanyanskyy Distric | Kiev | Ukraine | ||
| 82 | Regional Clinical Hospital | Vinnytsya | Ukraine |
Sponsors and Collaborators
- Galapagos NV
Investigators
- Study Director: Galapagos Study Director, Galapagos NV
Study Documents (Full-Text)
More Information
Publications
None provided.- GLPG0634-CL-204 (DARWIN2)
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at study sites in Latin America, Europe, United States, and New Zealand. The first participant was screened on 08 October 2013. The last study visit occurred on 29 May 2015. |
|---|---|
| Pre-assignment Detail | A total of 625 participants were screened of which 287 participants were randomized into the study and only 283 participants were treated. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, once daily (QD) during Weeks 1 to 12 and GLPG0634 100 milligram (mg) QD 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 percent [%] 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. |
| Period Title: Period 1 (Baseline up to Week 12) | ||||
| STARTED | 72 | 72 | 70 | 69 |
| COMPLETED | 65 | 67 | 67 | 66 |
| NOT COMPLETED | 7 | 5 | 3 | 3 |
| Period Title: Period 1 (Baseline up to Week 12) | ||||
| STARTED | 0 | 52 | 147 | 66 |
| COMPLETED | 0 | 50 | 142 | 65 |
| NOT COMPLETED | 0 | 2 | 5 | 1 |
Baseline Characteristics
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg QD 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. | Total of all reporting groups |
| Overall Participants | 72 | 72 | 70 | 69 | 283 |
| Age (years) [Mean (Full Range) ] | |||||
| Mean (Full Range) [years] |
51.5
|
52.1
|
52.8
|
51.8
|
52.1
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
56
77.8%
|
62
86.1%
|
53
75.7%
|
60
87%
|
231
81.6%
|
| Male |
16
22.2%
|
10
13.9%
|
17
24.3%
|
9
13%
|
52
18.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
25
34.7%
|
23
31.9%
|
25
35.7%
|
25
36.2%
|
98
34.6%
|
| Not Hispanic or Latino |
47
65.3%
|
49
68.1%
|
45
64.3%
|
44
63.8%
|
185
65.4%
|
| Unknown or Not Reported |
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%
|
| Asian |
0
0%
|
1
1.4%
|
0
0%
|
0
0%
|
1
0.4%
|
| Native Hawaiian or Other Pacific Islander |
1
1.4%
|
0
0%
|
0
0%
|
0
0%
|
1
0.4%
|
| Black or African American |
1
1.4%
|
1
1.4%
|
1
1.4%
|
0
0%
|
3
1.1%
|
| White |
53
73.6%
|
53
73.6%
|
53
75.7%
|
54
78.3%
|
213
75.3%
|
| More than one race |
17
23.6%
|
17
23.6%
|
16
22.9%
|
15
21.7%
|
65
23%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Rheumatoid Arthritis (RA) duration (years) [Mean (Full Range) ] | |||||
| Mean (Full Range) [years] |
9.46
|
8.63
|
8.57
|
8.68
|
8.84
|
| C-reactive protein (CRP) at Baseline (milligram per liter (mg/L)) [Mean (Full Range) ] | |||||
| Mean (Full Range) [milligram per liter (mg/L)] |
35.26
|
24.67
|
25.55
|
23.16
|
27.21
|
| Corrected tender joint count based on 68 joints (TJC68) at Baseline (joint count) [Mean (Full Range) ] | |||||
| Mean (Full Range) [joint count] |
25.226
|
25.58
|
27.195
|
26.242
|
26.051
|
| Corrected swollen joint count based on 66 joints (SJC66) at Baseline (joint count) [Mean (Full Range) ] | |||||
| Mean (Full Range) [joint count] |
15.98
|
16.969
|
18.653
|
15.74
|
16.834
|
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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg, QD 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. |
| Measure Participants | 72 | 72 | 70 | 69 |
| Number [percentage of participants] |
29.2
40.6%
|
66.7
92.6%
|
65.7
93.9%
|
72.5
105.1%
|
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 | < 0.0001 |
| 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 | 37.5 | |
| Confidence Interval |
(2-Sided) 95% 22.4 to 52.6 |
|
| 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 | < 0.0001 |
| 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 | 36.5 | |
| Confidence Interval |
(2-Sided) 95% 21.3 to 51.8 |
|
| 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 | < 0.0001 |
| 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 | 43.3 | |
| Confidence Interval |
(2-Sided) 95% 28.4 to 58.2 |
|
| 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 |
|---|
| All patients from the ITT population who were randomized to a GLPG0634 arm. The data for participants switching from placebo to GLPG0634 100 mg at Week 12 were not in scope for this analysis and were not reported. |
| Arm/Group Title | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD |
|---|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 72 | 70 | 69 |
| Number [percentage of participants] |
56.9
79%
|
78.6
109.2%
|
66.7
95.3%
|
| 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24. |
| 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg, QD 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. |
| Measure Participants | 72 | 72 | 70 | 69 |
| Week 1 |
1.4
1.9%
|
1.4
1.9%
|
10
14.3%
|
7.2
10.4%
|
| Week 2 |
4.2
5.8%
|
5.6
7.8%
|
7.1
10.1%
|
21.7
31.4%
|
| Week 4 |
4.2
5.8%
|
15.3
21.3%
|
18.6
26.6%
|
23.2
33.6%
|
| Week 8 |
5.6
7.8%
|
16.7
23.2%
|
25.7
36.7%
|
31.9
46.2%
|
| Week 12 |
11.1
15.4%
|
34.7
48.2%
|
37.1
53%
|
43.5
63%
|
| Week 24 |
33.3
46.3%
|
38.6
53.6%
|
44.9
64.1%
|
| 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24. |
| 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg QD 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. |
| Measure Participants | 72 | 72 | 70 | 69 |
| Week 1 |
0
0%
|
0
0%
|
1.4
2%
|
1.4
2%
|
| Week 2 |
2.8
3.9%
|
1.4
1.9%
|
1.4
2%
|
4.3
6.2%
|
| Week 4 |
1.4
1.9%
|
8.3
11.5%
|
5.7
8.1%
|
11.6
16.8%
|
| Week 8 |
2.8
3.9%
|
6.9
9.6%
|
11.4
16.3%
|
17.4
25.2%
|
| Week 12 |
2.8
3.9%
|
8.3
11.5%
|
18.6
26.6%
|
13
18.8%
|
| Week 24 |
19.4
26.9%
|
25.7
35.7%
|
24.6
35.1%
|
| 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). All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24. |
| 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg QD 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. |
| Measure Participants | 72 | 72 | 70 | 69 |
| Week 1 |
6.79
(1.34)
|
11.66
(1.641)
|
12.84
(2.291)
|
16.8
(2.346)
|
| Week 2 |
10.79
(1.917)
|
17.11
(2.362)
|
16.06
(2.261)
|
27.01
(2.776)
|
| Week 4 |
12.03
(2.058)
|
25
(2.852)
|
24.06
(2.898)
|
32.21
(3.172)
|
| Week 8 |
13.35
(2.24)
|
30.46
(2.986)
|
32.66
(3.154)
|
39.24
(3.375)
|
| Week 12 |
16.28
(2.723)
|
35.03
(3.178)
|
38.35
(3.533)
|
41
(3.477)
|
| Week 24 |
38.75
(3.748)
|
46.32
(3.295)
|
46.78
(3.648)
|
| 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24. |
| 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg QD 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. |
| Measure Participants | 72 | 72 | 70 | 69 |
| Week 1: None |
72
100%
|
57
79.2%
|
63
90%
|
49
71%
|
| Week 1: Moderate |
26
36.1%
|
40
55.6%
|
31
44.3%
|
43
62.3%
|
| Week 1: Good |
1
1.4%
|
3
4.2%
|
6
8.6%
|
7
10.1%
|
| Week 2: None |
67
93.1%
|
44
61.1%
|
47
67.1%
|
26
37.7%
|
| Week 2: Moderate |
31
43.1%
|
49
68.1%
|
46
65.7%
|
64
92.8%
|
| Week 2: Good |
3
4.2%
|
7
9.7%
|
7
10%
|
10
14.5%
|
| Week 4: None |
58
80.6%
|
38
52.8%
|
39
55.7%
|
22
31.9%
|
| Week 4: Moderate |
35
48.6%
|
47
65.3%
|
46
65.7%
|
55
79.7%
|
| Week 4: Good |
7
9.7%
|
15
20.8%
|
16
22.9%
|
23
33.3%
|
| Week 8: None |
54
75%
|
36
50%
|
24
34.3%
|
12
17.4%
|
| Week 8: Moderate |
36
50%
|
39
54.2%
|
54
77.1%
|
54
78.3%
|
| Week 8: Good |
10
13.9%
|
25
34.7%
|
21
30%
|
35
50.7%
|
| Week 12: None |
49
68.1%
|
31
43.1%
|
20
28.6%
|
14
20.3%
|
| Week 12: Moderate |
38
52.8%
|
46
63.9%
|
53
75.7%
|
41
59.4%
|
| Week 12: Good |
14
19.4%
|
24
33.3%
|
27
38.6%
|
45
65.2%
|
| Week 24: None |
28
38.9%
|
9
12.5%
|
10
14.3%
|
|
| Week 24: Moderate |
36
50%
|
41
56.9%
|
43
61.4%
|
|
| Week 24: Good |
36
50%
|
50
69.4%
|
46
65.7%
|
| 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24. |
| Time Frame | Weeks 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg QD 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. |
| Measure Participants | 72 | 72 | 70 | 69 |
| Week 4 |
0
0%
|
1.4
1.9%
|
0
0%
|
1.4
2%
|
| Week 8 |
0
0%
|
0
0%
|
0
0%
|
7.2
10.4%
|
| Week 12 |
1.4
1.9%
|
1.4
1.9%
|
4.3
6.1%
|
4.3
6.2%
|
| Week 24 |
8.3
11.5%
|
8.6
11.9%
|
8.7
12.4%
|
| 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24. |
| 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg QD 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. |
| Measure Participants | 71 | 70 | 70 | 68 |
| Baseline |
45.73
(1.4789)
|
43.77
(1.5609)
|
46.608
(1.6538)
|
44.139
(1.5079)
|
| Change at Week 1 |
-7.45
(1.5528)
|
9.596
(1.2567)
|
-10.886
(1.6511)
|
-14.349
(1.4346)
|
| Change at Week 2 |
-10.022
(1.371)
|
-12.194
(1.5982)
|
-13.172
(1.6209)
|
-18.27
(1.6934)
|
| Change at Week 4 |
-10.927
(1.7771)
|
-17.57
(1.7653)
|
-18.862
(1.8073)
|
-21.288
(1.6619)
|
| Change at Week 8 |
-12.452
(1.7748)
|
-20.144
(1.9425)
|
-23.119
(1.8041)
|
-25.556
(1.6949)
|
| Change at Week 12 |
-12.574
(1.984)
|
-21.413
(1.7953)
|
-25.269
(1.9856)
|
-26.499
(1.7534)
|
| Change at Week 24 |
-23.16
(1.9364)
|
-30.983
(1.7732)
|
-29.564
(1.8583)
|
| 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24. |
| 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg QD 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. |
| Measure Participants | 71 | 70 | 70 | 68 |
| Baseline |
42.168
(1.3272)
|
41.438
(1.4777)
|
44.052
(1.5383)
|
41.869
(1.423)
|
| Change at Week 1 |
-6.867
(1.4538)
|
-9.226
(1.1545)
|
-9.853
(1.5591)
|
-13.148
(1.4085)
|
| Change at Week 2 |
-9.861
(1.1909)
|
-11.803
(1.5275)
|
-12.306
(1.5618)
|
-16.999
(1.702)
|
| Change at Week 4 |
-10.743
(1.7184)
|
-16.701
(1.7003)
|
-17.654
(1.6987)
|
-20.044
(1.6396)
|
| Change at Week 8 |
-12.071
(1.6982)
|
-19.087
(1.8583)
|
-21.703
(1.7491)
|
-24.228
(1.6479)
|
| Change at Week 12 |
11.696
(1.8752)
|
-21.019
(1.7168)
|
-24.044
(1.9665)
|
-25.071
(1.742)
|
| Change at Week 24 |
-22.278
(1.8637)
|
-29.502
(1.6928)
|
-28.102
(1.818)
|
| 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24. |
| 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24. |
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg QD 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. |
| Measure Participants | 71 | 70 | 70 | 69 |
| Baseline |
25.1
(1.12)
|
25.1
(1.28)
|
24.8
(1.13)
|
24.8
(1.16)
|
| Change at Week 4 |
1.4
(1.14)
|
7.2
(1.3)
|
7.2
(1.26)
|
8.5
(1.3)
|
| Change at Week 12 |
3.9
(1.23)
|
9.5
(1.43)
|
10.2
(1.21)
|
11.2
(1.44)
|
| Change at Week 24 |
10
(1.43)
|
11.3
(1.2)
|
13.7
(1.38)
|
| 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. All placebo participants switched to GLPG0634 treatment at Week 12 and were not included in the analysis of Week 24. |
| 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg QD 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. |
| Measure Participants | 71 | 70 | 70 | 69 |
| PCS at Baseline |
31.1
(0.6988)
|
31.05
(0.816)
|
30.946
(0.7631)
|
31.804
(0.8965)
|
| PCS Change at Week 4 |
2.1
(0.72)
|
5.7
(1.04)
|
5.1
(0.92)
|
6.8
(0.92)
|
| PCS Change at Week 12 |
3
(0.89)
|
7.1
(1.11)
|
7.8
(1.04)
|
8.6
(1.09)
|
| PCS Change at Week 24 |
6.9
(1.16)
|
10
(1.17)
|
9.7
(1.09)
|
|
| MCS at Baseline |
40.525
(1.3053)
|
42.793
(1.3247)
|
41.185
(1.2347)
|
42.613
(1.1674)
|
| MCS at Week 4 |
2.1
(1.1)
|
3.6
(1.09)
|
5.3
(1.04)
|
3.9
(1.16)
|
| MCS at Week 12 |
2.7
(1.04)
|
4.9
(1.18)
|
6.9
(1.04)
|
6.8
(1.33)
|
| MCS at Week 24 |
5.1
(1.27)
|
7.7
(1.16)
|
8.5
(1.12)
|
Adverse Events
| Time Frame | Baseline through end of study drug treatment (average exposure: 161.0 days) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Nonresponders from 50 mg QD (15 participants) moved to 100 mg QD group for Week 13 to 24. | |||||||
| Arm/Group Title | Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | ||||
| Arm/Group Description | Participants received GLPG0634 matching placebo capsules, orally, QD during Weeks 1 to 12 and GLPG0634 100 mg QD 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. | ||||
All Cause Mortality |
||||||||
| Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/72 (0%) | 0/72 (0%) | 0/85 (0%) | 0/69 (0%) | ||||
Serious Adverse Events |
||||||||
| Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/72 (1.4%) | 2/72 (2.8%) | 3/85 (3.5%) | 3/69 (4.3%) | ||||
| Ear and labyrinth disorders | ||||||||
| Vertigo | 0/72 (0%) | 0/72 (0%) | 1/85 (1.2%) | 0/69 (0%) | ||||
| Infections and infestations | ||||||||
| Cellulitis | 0/72 (0%) | 0/72 (0%) | 1/85 (1.2%) | 0/69 (0%) | ||||
| Gastroenteritis | 0/72 (0%) | 1/72 (1.4%) | 0/85 (0%) | 0/69 (0%) | ||||
| Pneumonia | 0/72 (0%) | 0/72 (0%) | 0/85 (0%) | 1/69 (1.4%) | ||||
| Pyelonephritis chronic | 0/72 (0%) | 0/72 (0%) | 1/85 (1.2%) | 0/69 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Humerus fracture | 0/72 (0%) | 1/72 (1.4%) | 0/85 (0%) | 0/69 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/72 (0%) | 0/72 (0%) | 0/85 (0%) | 1/69 (1.4%) | ||||
| Osteoarthritis | 0/72 (0%) | 0/72 (0%) | 0/85 (0%) | 1/69 (1.4%) | ||||
| Rheumatoid arthritis | 1/72 (1.4%) | 0/72 (0%) | 0/85 (0%) | 0/69 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | GLPG0634 50 mg QD | GLPG0634 100 mg QD | GLPG0634 200 mg QD | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/72 (12.5%) | 14/72 (19.4%) | 21/85 (24.7%) | 16/69 (23.2%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/72 (0%) | 1/72 (1.4%) | 0/85 (0%) | 4/69 (5.8%) | ||||
| Infections and infestations | ||||||||
| Upper respiratory tract infection | 2/72 (2.8%) | 2/72 (2.8%) | 4/85 (4.7%) | 4/69 (5.8%) | ||||
| Urinary tract infection | 1/72 (1.4%) | 3/72 (4.2%) | 7/85 (8.2%) | 4/69 (5.8%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypercholesterolaemia | 3/72 (4.2%) | 4/72 (5.6%) | 5/85 (5.9%) | 1/69 (1.4%) | ||||
| Hypertriglyceridaemia | 1/72 (1.4%) | 2/72 (2.8%) | 5/85 (5.9%) | 1/69 (1.4%) | ||||
| Nervous system disorders | ||||||||
| Headache | 1/72 (1.4%) | 4/72 (5.6%) | 1/85 (1.2%) | 3/69 (4.3%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 4/72 (5.6%) | 3/72 (4.2%) | 1/85 (1.2%) | 2/69 (2.9%) | ||||
Limitations/Caveats
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 |
- GLPG0634-CL-204 (DARWIN2)