Long-term Follow-up Study of GLPG0634 in Active Rheumatoid Arthritis Participants

Rheumatoid Arthritis Clinical Trial

— DARWIN3  

Official title:

A Multicenter, Open-label, Long-term Follow-up Safety and Efficacy Study of GLPG0634 Treatment in Subjects With Moderately to Severely Active Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02065700
• Other study ID #: GLPG0634-CL-205
• Secondary ID: 2012-003655-11
• Status: Completed
• Phase: Phase 2
• Start date: February 25, 2014
• Est. completion date: January 19, 2023

Study information

• Verified date: May 2024
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study was to evaluate the long-term safety and tolerability of filgotinib (formerly GLPG0634) for the treatment of rheumatoid arthritis.

Participants were enrolled in this open-label long-term follow-up study after they had completed one of the two core studies, GLPG0634-CL-203 (DARWIN1) (NCT01888874) or GLPG0634-CL-204 (DARWIN2) (NCT01894516), and were evaluated for any side effects that might have occured (long-term safety and tolerability) when taking filgotinib. During the course of the study, participants were also examined for long-term effects of filgotinib administration on disease activity (efficacy), participant's disability, fatigue, and quality of life.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 739
• Est. completion date: January 19, 2023
• Est. primary completion date: January 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Participants who completed one of the qualifying core studies GLPG0634-CL-203 or GLPG0634-CL-204 and may benefit from filgotinib long-term treatment according to the Investigator's judgment

• Females of childbearing potential and sexually active men must agree to use highly effective method of birth control as specified in the protocol, during the study and for at least 12 weeks after the last dose of filgotinib

Key Exclusion Criteria:

• Participants who prematurely withdrew from one of the 2 core studies (GLPG0634-CL-203 or GLPG0634-CL-204), for any reason

• Persistent abnormal lab values during one of the 2 core studies (GLPG0634-CL-203 or GLPG0634-CL-204), according to the Investigator's judgment

• Diagnosis of rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis, except for secondary Sjogren's syndrome

• Any condition or circumstances which, in the opinion of the Investigator, may make a participant unlikely or unable to complete the study or comply with study procedures and requirements

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Filgotinib
Administered as Oral Tablets

Locations

Country	Name	City	State
Argentina	Atencion Integral en Reumatologa	Buenos Aires
Argentina	CER Intituto Medico	Buenos Aires
Argentina	Organizacion Medica de Investigaciones (OMI)	Buenos Aires
Argentina	Instituto Reumatologico Strusberg	Cordoba
Argentina	CIMeL Centro dee Investigacion Medico Lanus	Lanus
Argentina	Instituto CAICI	Rosario
Argentina	Instituto de Asistencia Reumatologia Integral - IARI	San Fernando
Argentina	Centro Médico Privado de Reumatologia	San Miguel de Tucumán
Australia	Flinders Medical Centre	Bedford Park	Flinders Drive, South Australia
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba
Belgium	Cliniques Universitaires St-Luc	Brussels
Belgium	UZ Leuven	Leuven
Bulgaria	University "Multiprofile Hospital for Active Treatment - Kaspela" LTD	Plovdiv
Bulgaria	Multiprofile Hospital for Active Treatment - Ruse	Ruse
Bulgaria	Diagnostic Consultative Center "Sveta Anna" LTD	Sofia
Bulgaria	National Multiprofile Transport Hospital "Tsar Boris III," Sofia, Clinical of Internal Diseases	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment "SV. Ivan Rilski" EAD, Sofia, Rheumatology Clinic	Sofia
Chile	Hospital Regional "Guillermo Grant Benavente"	Santiago
Chile	Prosalud	Santiago
Chile	Someal SA	Santiago
Chile	Centro de Investigacion Clinica del Sur	Temuco
Chile	Consulta Privada Dra. Ponce	Temuco
Colombia	Circaribe S.A.S	Barranquilla
Colombia	Centro de Investigacion en Reumatologia y Especialidades Medicas (CIREEM)	Bogota
Colombia	Idearg Sas	Bogota
Colombia	Riesgo De Fractura Cayre Ips7	Bogotá
Colombia	Medicity S.A.S.	Bucaramanga	Santander
Colombia	Preventive Care SAS	Cundinamarca
Colombia	Hospital Pablo Tobon Uribe	Medellin
Czechia	Revmatologie S.R.O	Brno
Czechia	Revmatologicka a interni ambulance	Kladno
Czechia	Revmatologicka ambulance	Praha-Nusle
Czechia	PV-Medical S.R.O.	Zlin
France	Hospitaux de Hautepierre	Strasbourg CEDEX
Germany	Schlossparkklinik - Akad. Lehrkrankenhaus Charite	Berlin
Germany	MVZ Rheumatologie and Autoimmun Medizin HH GmbH	Hamburg
Guatemala	Clinica de Especialidades Medicas	Guatemala
Guatemala	Clinica Medica	Guatemala
Guatemala	Clinica Medica Especializada en Reumatologia	Guatemala
Guatemala	Reuma S.A.	Guatemala
Guatemala	Reuma-Centro	Guatemala
Guatemala	Centro Clinico	Guatemala City
Hungary	Gyogyszervizs galo Kozpont Kft	Balatonfured
Hungary	QualiClinic Kft.	Budapest
Hungary	Reumatologiai Kft.	Budapest
Hungary	Markhot Ferenc Hospital, Rheumatology	Eger
Hungary	Csolnoky Ferenc Hospital, Rheumatology	Veszprem
Israel	Carmel Medical Center	Haifa
Israel	Rambam Medical Center	Haifa
Latvia	Ltd M&M Centr	Adazi
Latvia	SIA Arijas Ancane's Family Doctor	Baldone
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	L. Atikes doktorats	Liepaja
Latvia	'Bruninieku' polyclinic	Riga
Mexico	Centro Medico Dalinde	Ciudad de Mexico
Mexico	Centro de Estudios de Investigacion Basica y Clinica, SC	Guadalajara
Mexico	Arke Estudios Clinicos S.A. de C.V.	Mexico
Mexico	Clinstile, S.A. de C.V.	Mexico
Mexico	Hospital General de México	Mexico
Mexico	Hospital Universitario José E. Gonzalez	Monterrey
Mexico	OSMO	Oaxaca
Moldova, Republic of	IMSP Institutul de Cardiologie	Chisinau
New Zealand	Waikato Hospital	Hamilton
New Zealand	Timaru Rheumatology Studies	Timaru
Poland	NZOZ Osteo-Medic s.c.	Bialystok
Poland	Centrum Medyczne Silesiana Sp. Z.o.o.	Bytom
Poland	Centrum Medyczne Pratia Katowice	Katowice
Poland	Centrum Medyczne Plejady	Krakow
Poland	NZOZ "DOBRY LEKARZ" Specjalistyczne Poradnie Lekarskie	Krakow
Poland	Specjalistyczne Centrum Medyczne Nowomed	Krakow
Poland	NZOZ Przychodnia Lekarska "Eskulap"	Skierniewice
Poland	Powiatowy Zaklad Opieki Zdrowotnej w Starachowicach	Starachowice
Poland	NZOZ "Nasz Lekarz" Pratyka Grupowa Lekarzy Rodzinnychz	Torun
Poland	AMED Medical Center	Warsaw
Poland	Rheumatica Sp. Z.o.o.	Warszawa
Romania	Spitalul Clinic Sfanta Maria	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta Sf. Apostol Andrei Galati	Galati
Russian Federation	First Moscow State Medical University n.a. I.M. Sechenova of the Ministry of Health	Moscow
Russian Federation	Scientific Research Institute of Rheumatology	Moscow
Russian Federation	City Clinical Hospital #5	Nizhniy Novgorod
Russian Federation	GBOU VPO Orenburg State Medical University	Orenburg
Russian Federation	Ryazan State Medical University	Ryazan
Russian Federation	Regional Clinical Hospital	Saratov
Russian Federation	City Hospital #26	St Petersburg
Russian Federation	Vladimir Regional State Instituion of Healthcare	Vladimir
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC)	A Coruña
Spain	Sanatorio Nuestra Señora de la Esperanza	A Coruña
Spain	Hospital Parc Tauli	Sabadell
Ukraine	Communal Institution of Healthcare - Kharkiv City Clinical Hospital #13	Kharkiv
Ukraine	Kharkiv Medical Academy of Postgraduate Education, Department of Cardiology	Kharkiv
Ukraine	L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine	Kharkiv
Ukraine	Kherson City Clinical Hospital N. A. Afanasii and Olga Tropin	Kherson
Ukraine	Municipal Non-Profit Institution Consultative and Diagnostic Centre of Desnyasky District of Kyiv	Kiev
Ukraine	Municipal Non-profit Enterprise Consultative and Diagnostic Center of Pechersk District of Kiev city	Kyiv
Ukraine	Vinnitsya Regional Clinical Hospital Named after M.I.Pirogov, Rheumatology Department	Vinnytsya
United States	Austin Rheumatology Research PA	Austin	Texas
United States	RASF Clinical Research Center	Boca Raton	Florida
United States	Low County Rheumatology PA	Charleston	South Carolina
United States	Arthro, Arthritis Care & Research	Gilbert	Arizona
United States	Physicians East	Greenville	North Carolina
United States	Klein and Associates MD, PA	Hagerstown	Maryland
United States	C.V. Mehta MD Medical Corp.	Hemet	California
United States	Pioneer Research Solutions Inc	Houston	Texas
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Arizona Arthritis & Rheumatology Research PLLC	Mesa	Arizona
United States	Health Research of Oklahoma	Oklahoma City	Oklahoma
United States	Millenium Research	Ormond Beach	Florida
United States	Desert Medical Advances	Palm Desert	California
United States	Springfield Clinic	Springfield	Illinois
United States	Lovelace Scientific Resources	Venice	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Galapagos NV	Gilead Sciences

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Bulgaria,  Chile,  Colombia,  Czechia,  France,  Germany,  Guatemala,  Hungary,  Israel,  Latvia,  Mexico,  Moldova, Republic of,  New Zealand,  Poland,  Romania,  Russian Federation,  Spain,  Ukraine, 

References & Publications (5)

Genovese MC, Kavanaugh A, Winthrop K, et al. Long Term Safety of Filgotinib in the Treatment of Rheumatoid Arthritis: Week 84 Data from a Phase 2b Open-Label Extension Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10).

Kavanaugh A, Genovese MC, Winthrop K, et al. Rheumatoid Arthritis Treatment with Filgotinib: Week 132 Safety Data from a Phase 2b Open-Label Extension Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9).

Kavanaugh A, Westhovens R, Winthrop K, et al. Rheumatoid Arthritis Treatment with Filgotinib: Week 156 Safety and Efficacy Data from a Phase 2b Open-Label Extension Study [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10).

Kavanaugh A, Westhovens RR, Winthrop KL, Lee SJ, Tan Y, An D, Ye L, Sundy JS, Besuyen R, Meuleners L, Stanislavchuk M, Spindler AJ, Greenwald M, Alten R, Genovese MC. Safety and Efficacy of Filgotinib: Up to 4-year Results From an Open-label Extension Stu — View Citation

R. Westhovens, R. Alten, K. Winthrop, et al. Long term safety of filgotinib in the treatment of rheumatoid arthritis: week 108 data from a phase 2b open-label extension study. [abstract]. Ann Rheum Dis. 2018;77 (suppl 2)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Treatment-Emergent Adverse Events	An Adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.; Treatment-emergent adverse events (TEAEs) were defined as any AEs with an onset date on or after the filgotinib start date in the core studies or GLPG0634-CL-205 (NCT02065700), and no later than 30 days after permanent discontinuation of filgotinib in GLPG0634-CL-205 (NCT02065700) or of either 30 days after the last dose date.	From First dose to Week 437
Secondary	Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response: Non-Responder Imputation (NRI)	The American College of Rheumatology (ACR) response was a measurement of improvement in multiple disease assessment criteria.; The ACR20 response was defined as: 1) = 20% improvement from baseline in swollen joint count 66 (SJC66), and 2) = 20% improvement from baseline in tender joint count 68 (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.Subject's Global Assessment of Disease Activity (SGA) (VAS), 3. Physician's Global Assessment of Disease Activity (PGA) (VAS), 4. Total HAQ-DI score, and 5. High-Sensitivity C- Reactive Protein (hsCRP).	Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Percentage of Participants Achieving ACR20 Response: Observed Case (OC)	The ACR response was a measurement of improvement in multiple disease assessment criteria.; The ACR20 response was 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 VAS (taken from the HAQ-DI), 2.SGA (VAS), 3. PGA (VAS), 4. Total HAQ-DI score, and 5. hsCRP.	Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Percentage of Participants Achieving ACR50 Response: NRI	The ACR response was a measurement of improvement in multiple disease assessment criteria.; 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.SGA (VAS) 3. PGA (VAS) 4. Total HAQ-DI score 5. hsCRP.	Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Percentage of Participants Achieving ACR50 Response: OC	The ACR response was a measurement of improvement in multiple disease assessment criteria.; 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.SGA (VAS) 3. PGA (VAS) 4. Total HAQ-DI score 5. hsCRP.	Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Percentage of Participants Achieving ACR70 Response: NRI	The ACR response was a measurement of improvement in multiple disease assessment criteria.; ACR70 response was defined as : 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.SGA (VAS), 3. PGA (VAS), 4. Total HAQ-DI score, and 5. hsCRP.	Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Percentage of Participants Achieving ACR70 Response: OC	The ACR response was a measurement of improvement in multiple disease assessment criteria.; ACR70 response was defined as : 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.SGA (VAS), 3. PGA (VAS), 4. Total HAQ-DI score, and 5.hsCRP.	Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	ACR N% Improvement (ACR-N) Response: OC	ACR-N was defined as the smallest percentage improvement from core baseline in SJC66, TJC68 and the median of the following 5 items (Pain VAS [taken from the HAQ-DI], 2.SGA (VAS), 3. PGA (VAS), 4. Total HAQ-DI score, and 5. hsCRP). It had a range between 0 and 100%.	Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Change From Core Baseline in Disease Activity Score Based on 28 Joints Using C-reactive Protein (DAS28[CRP]): OC	The DAS28(CRP) was a measure of the participant's disease activity calculated using the TJC (28 joints), SJC (28 joints), SGA [using a VAS on a scale of 0 (very well) to 100 (very poor)] and hsCRP using the formula: DAS28(CRP) = 0.56 * Square root [SQRT] (TJC28) + 0.28 * SQRT(SJC28) + 0.36 * Ln(CRP+1) + 0.014 * SGA + 0.96; and the total possible score ranged from 1 to 9.4. Higher values indicated higher disease activity. A negative change from baseline indicated improvement.	Core Baseline, Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Change From Core Baseline in Simple Disease Activity Index (SDAI): OC	SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA (0 to 10 cm), PGA (0 to 10 cm), CRP (mg/dL). SDAI = TJC + SJC + SGA + PGA+ CRP. The SDAI score ranged from 0 to approximately 86. Higher SDAI indicated greater disease activity. A negative change from baseline indicated improvement.	Core Baseline, Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Change From Core Baseline in Clinical Disease Activity Index (CDAI): OC	The CDAI was the SDAI modified that excluded CRP and consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA (0 to 10 cm), PGA (0 to 10 cm). SDAI = TJC + SJC + SGA+ PGA. The CDAI score ranged from 0 to approximately 76. Higher CDAI indicated greater disease activity. A negative change from baseline indicated improvement.	Core Baseline, Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Response: OC	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.	Core Baseline, Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Percentage of Participants Achieving ACR/EULAR Remission: NRI	A participant's disease activity status was defined as being in remission when scores on the TJC28, SJC28, CRP (actual value in mg/dL) and SGA (cm) were all = 1.	Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Percentage of Participants Achieving ACR/EULAR Remission: OC	A participant's disease activity status was defined as being in remission when scores on the TJC28, SJC28, CRP (actual value in mg/dL) and SGA (cm) were all = 1.	Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408
Secondary	Change From Core Baseline in Physical Component Score (PCS) of Quality of Life Using the Short Form-36 (SF-36) Scores: OC	The health-related quality of life of the subject was assessed using the SF-36 with a 4-week recall period. This consists of 36 questions belonging to 8 domains in 2 components: Physical well-being: 4 domains: physical functioning (10 items), role physical (4 items), bodily pain (2 items), and general health (GH) perceptions (5 items).; Mental well-being: 4 domains: vitality (4 items), social functioning (2 items), role emotional (3 items), and mental health (5 items).; These scales were from 0 to 100 with higher scores indicating a better quality of life.	Core Baseline, Extension Baseline, Weeks 48, 96, 144, 192, 240, 288, 336, 384
Secondary	Change From Core Baseline in MCS of Quality of Life Using the SF-36 Scores: OC	The health-related quality of life of the subject was assessed using the SF-36 with a 4-week recall period. This consists of 36 questions belonging to 8 domains in 2 components: Physical well-being: 4 domains: physical functioning (10 items), role physical (4 items), bodily pain (2 items), and general health (GH) perceptions (5 items).; Mental well-being: 4 domains: vitality (4 items), social functioning (2 items), role emotional (3 items), and mental health (5 items).; These scales were from 0 to 100 with higher scores indicating a better quality of life.	Core Baseline, Extension Baseline, Weeks 48, 96, 144, 192, 240, 288, 336, 384
Secondary	Change From Core Baseline in Quality of Life Using Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale: OC	FACIT-Fatigue scale was a 13-item questionnaire, each scored on a 5-point scale: 0 (Not at all) to 4 (Very much). Negatively stated items were reversed by subtracting the response from "4" before being added to obtain a total score. 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 less fatigue. A positive change from baseline indicated better quality of life.	Core Baseline, Extension Baseline, Weeks 48, 96, 144, 192, 240, 288, 336, 384