Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis
10. Dezember 2020 aktualisiert von: GlaxoSmithKline
A Phase IIb, Double-Blind, Placebo-Controlled, Dose-Adaptive, Study of the Efficacy and Safety of GSK3196165 in Combination With Methotrexate Therapy, in Subjects With Active Moderate-Severe Rheumatoid Arthritis Despite Treatment With Methotrexate
This is a randomised, Phase IIb, dose-adaptive, multicentre, double-blind, parallel group, placebo-controlled study with the primary objective to assess the efficacy of GSK3196165, in combination with methotrexate (MTX), in subjects with active moderate severe rheumatoid arthritis (RA) despite treatment with MTX.
Approximately 210 subjects will be randomised into the study, following a screening period of up to four weeks.
The total treatment period is up to 52 weeks, with a 12-week follow-up period after the last dose (Week 50).
Subjects will be randomised (1:1:1:1:1:1) to placebo or one of five subcutaneous (SC) GSK3196165 doses, in combination with MTX (at a weekly dose between 15-25 milligram [mg]), previously received for at least 12 weeks, with a stable and tolerated dose and route of administration for >=4 weeks.
Escape therapy is provided at specified timepoints in the protocol for subjects that do not achieve adequate disease improvement.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Studientyp
Interventionell
Einschreibung (Tatsächlich)
222
Phase
- Phase 2
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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Plovdiv, Bulgarien, 4000
- GSK Investigational Site
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Plovdiv, Bulgarien, 4002
- GSK Investigational Site
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Sofia, Bulgarien, 1431
- GSK Investigational Site
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Sofia, Bulgarien, 1606
- GSK Investigational Site
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Bad Doberan, Deutschland, 18209
- GSK Investigational Site
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Berlin, Deutschland, 14059
- GSK Investigational Site
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Hamburg, Deutschland, D-20095
- GSK Investigational Site
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Nordrhein-Westfalen
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Koeln, Nordrhein-Westfalen, Deutschland, 50937
- GSK Investigational Site
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Tallinn, Estland, 10117
- GSK Investigational Site
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Tallinn, Estland, 13419
- GSK Investigational Site
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Bologna, Italien, 40138
- GSK Investigational Site
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Napoli, Italien, 80131
- GSK Investigational Site
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Lombardia
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Milano, Lombardia, Italien, 20132
- GSK Investigational Site
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Barrie, Kanada, L4M 6L2
- GSK Investigational Site
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Ontario
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Brampton, Ontario, Kanada, L6T 0G1
- GSK Investigational Site
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San Luis Potosí, Mexiko, 78213
- GSK Investigational Site
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Jalisco
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Guadalajara, Jalisco, Mexiko, 44650
- GSK Investigational Site
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Morelos
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Cuernavaca, Morelos, Mexiko, 62170
- GSK Investigational Site
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Cuernavaca, Morelos, Mexiko, 62290
- GSK Investigational Site
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Yucatán
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Merida, Yucatán, Mexiko, 97000
- GSK Investigational Site
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Bialystok, Polen, 15-351
- GSK Investigational Site
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Bydgoszcz, Polen, 85-168
- GSK Investigational Site
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Bytom, Polen, 41-902
- GSK Investigational Site
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Grodzisk Mazowiecki, Polen, 05-825
- GSK Investigational Site
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Lodz, Polen, 91-347
- GSK Investigational Site
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Lublin, Polen, 20-582
- GSK Investigational Site
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Torun, Polen, 87-100
- GSK Investigational Site
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Warszawa, Polen, 01-518
- GSK Investigational Site
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Warszawa, Polen, 02-653
- GSK Investigational Site
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Moscow, Russische Föderation, 119049
- GSK Investigational Site
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Novosibirsk, Russische Föderation, 630099
- GSK Investigational Site
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Omsk, Russische Föderation, 644111
- GSK Investigational Site
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Ryazan, Russische Föderation, 390026
- GSK Investigational Site
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Saint Petersburg, Russische Föderation, 192177
- GSK Investigational Site
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Tver, Russische Föderation, 170036
- GSK Investigational Site
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Vladimir, Russische Föderation, 600023
- GSK Investigational Site
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Yaroslavl, Russische Föderation, 150003
- GSK Investigational Site
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Yaroslavl, Russische Föderation, 150023
- GSK Investigational Site
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Coruña, Spanien, 15006
- GSK Investigational Site
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Madrid, Spanien, 28041
- GSK Investigational Site
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Panorama / Cape Town, Südafrika, 7500
- GSK Investigational Site
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Stellenbosch, Südafrika, 7600
- GSK Investigational Site
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Gauteng
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Pretoria, Gauteng, Südafrika, 1
- GSK Investigational Site
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Brno, Tschechien, 602 00
- GSK Investigational Site
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Bruntal, Tschechien, 792 01
- GSK Investigational Site
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Praha, Tschechien, 130 00
- GSK Investigational Site
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Praha 5, Tschechien, 150 06
- GSK Investigational Site
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Uherske Hradiste, Tschechien, 686 01
- GSK Investigational Site
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Ivano-Frankivsk, Ukraine, 76008
- GSK Investigational Site
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Kharkiv, Ukraine, 61029
- GSK Investigational Site
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Kharkiv, Ukraine, 61039
- GSK Investigational Site
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Kryvyi Rih, Ukraine, 50056
- GSK Investigational Site
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Lviv, Ukraine, 79013
- GSK Investigational Site
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Odesa, Ukraine, 65026
- GSK Investigational Site
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Poltava, Ukraine, 36011
- GSK Investigational Site
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Sumy, Ukraine, 40022
- GSK Investigational Site
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Vinnytsia, Ukraine, 21018
- GSK Investigational Site
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Vinnytsya, Ukraine, 21029
- GSK Investigational Site
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Zhytomyr, Ukraine, 10002
- GSK Investigational Site
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Budapest, Ungarn, 1036
- GSK Investigational Site
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Kistarcsa, Ungarn, 2143
- GSK Investigational Site
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Veszprém, Ungarn, 8200
- GSK Investigational Site
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Birmingham, Vereinigtes Königreich, B15 2TH
- GSK Investigational Site
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Leeds, Vereinigtes Königreich, LS7 4SA
- GSK Investigational Site
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre und älter (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
Inclusion Criteria:
- Age >=18 years at the time of signing informed consent.
- Meets ACR/EULAR 2010 RA Classification Criteria, with disease duration of >=12 weeks.
- Swollen joint count of >=4 (66-joint count) and tender joint count of >=4 (68-joint count).
- DAS28(CRP) >=3.2.
- CRP >=5.0 milligram per litre (mg/L) at screening.
- Must have previously received MTX (15-25 mg weekly) for at least 12 weeks before screening, with no change in route of administration, with a stable and tolerated dose for >=4 weeks prior to Day 1. A stable dose of MTX >=7.5 mg/week is acceptable, if the MTX dose has been reduced for reasons of documented intolerance to MTX, e.g. hepatic or hematologic toxicity, or per local requirement.
- Weight >=45 kilogram (kg).
- Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria.
- Diffusing capacity of the lung for carbon monoxide (DLCO) >=60% predicted; forced expiratory volume in 1 second (FEV1) >=70% predicted
- No evidence of active or latent infection with Mycobacterium tuberculosis (TB).
Exclusion Criteria:
- Pregnant or lactating women.
- History of other inflammatory rheumatological or autoimmune disorders, other than Sjögren's syndrome secondary to RA.
- History of any respiratory disease which (in the opinion of the investigator) would compromise subject safety or the ability of the subject to complete the study (e.g. significant interstitial lung disease, such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), moderate-severe asthma, bronchiectasis, previous pulmonary alveolar proteinosis [PAP]).
- Clinically-significant or unstable (in the opinion of the investigator) persistent cough or dyspnea that is unexplained.
- Significant unstable or uncontrolled acute or chronic disease which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.
- A history of malignancy.
- Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
- Current/previous Hepatitis B virus (HBV), Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) 1 or 2 infection.
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Doppelt
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: GSK3196165, Dose 1 + MTX and Folic acid
Subject will receive GSK3196165 Dose 1 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.
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GSK3196165 wird als Flüssigkeit geliefert und als SC-Injektion verabreicht.
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
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Experimental: GSK3196165, Dose 2 + MTX and folic acid
Subject will receive GSK3196165 Dose 2 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.
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GSK3196165 wird als Flüssigkeit geliefert und als SC-Injektion verabreicht.
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
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Experimental: GSK3196165, Dose 3 + MTX and folic acid
Subject will receive GSK3196165 Dose 3 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.
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GSK3196165 wird als Flüssigkeit geliefert und als SC-Injektion verabreicht.
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
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Experimental: GSK3196165, Dose 4 + MTX and folic acid
Subject will receive GSK3196165 Dose 4 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.
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GSK3196165 wird als Flüssigkeit geliefert und als SC-Injektion verabreicht.
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
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Experimental: GSK3196165, Dose 5 + MTX and folic acid
Subject will receive GSK3196165 Dose 5 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.
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GSK3196165 wird als Flüssigkeit geliefert und als SC-Injektion verabreicht.
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
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Placebo-Komparator: Placebo + MTX and folic acid
Subjects will receive placebo (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.
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MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
Placebo is supplied as liquid as sterile 0.9% weight by volume (w/v) sodium chloride solution and will be administered as SC injection
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Percentage of Participants Who Achieved Disease Activity Score for 28 Different Joints With C-reactive Protein Value (DAS28{CRP}) Remission (DAS28 <2.6) at Week 24
Zeitfenster: Week 24
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DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment.
DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96.
Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 millimeter [mm] visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in [milligrams/liter] mg/L).
It ranges between 0.96 and 8.61.
High score (worse outcome) and low scores (better outcome).
ITT population comprised of all participants who were randomized to treatment and who received at least one dose of study treatment (GSK3196165 or placebo).
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Week 24
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Change From Baseline in DAS28(CRP) at Week 12
Zeitfenster: Baseline and Week 12
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DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment.
DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96.
Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant global assessment of disease activity (PtGA) using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L).
It ranges between 0.96 and 8.61.
High score (worse outcome) and low scores (better outcome).
Baseline was defined as the last available assessment prior to the start of study treatment.
Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
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Baseline and Week 12
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Percentage of Participants Who Achieved DAS28(CRP) Remission (DAS28 <2.6) at All Time Points
Zeitfenster: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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DAS28(CRP) remission is defined as a DAS28 score of <2.6 points.
The DAS index combines information relating to the number of swollen and tender joints.
The DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment.
DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96.
Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L).
It ranges between 0.96 and 8.61.
High score (worse outcome) and low scores (better outcome).
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Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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Change From Baseline in DAS28(CRP) at All Assessment Time Points
Zeitfenster: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
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DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment.
DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96.
Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L).
It ranges between 0.96 and 8.61.
High score (worse outcome) and low scores (better outcome).
Baseline was defined as the last available assessment prior to the start of study treatment.
Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline.
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Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
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Time to First DAS28(CRP) Remission
Zeitfenster: Up to Week 62
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The DAS index combines information relating to the number of swollen and tender joints.
The DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment.
DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96.
Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L).
It ranges between 0.96 and 8.61.
High score (worse outcome) and low scores (better outcome).
Median time, to remission has been presented.
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Up to Week 62
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Percentage of Participants Achieving Categorical DAS28(CRP) Response (Moderate/Good [European League Against Rheumatism] EULAR Response) at All Assessment Time Points
Zeitfenster: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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DAS28(CRP) scores were categorized using EULAR response criteria.
Response at a given time point was defined based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to Baseline.
The definition of no response, moderate response and good response was as follows: Current DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2=good response), (>0.6 to <=1.2 = moderate response) and (<=0.6 =no response).
Current DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline value (>1.2 =moderate response), (>0.6 to <=1.2 = moderate response) and (<=0.6 =no response).
Current DAS28 >5.1 and DAS28 decrease from Baseline value (>1.2=moderate response), (>0.6 to <=1.2 = no response) and (<=0.6 =no response).
If the post-Baseline DAS28(CRP) score was missing, then the corresponding EULAR category was set to missing.
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Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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Percentage of Participants With American College of Rheumatology's (ACR) 20/50/70 Response Rates at All Assessment Time Points
Zeitfenster: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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The ACR definition for calculating improvement in rheumatoid arthritis is calculated as a 20% improvement (ACR20) in both tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR-core set measures: participant and physician global assessments, participant's assessment of arthritis pain, disability, and an acute-phase reactant (i.e.
CRP value).
Similarly, ACR50 and ACR70 were calculated with the respective percent improvement.
The specific components of the ACR assessments are as follows: Tender/Painful Joint count 68 (TJC68), Swollen Joint Count 66 (SJC66), Participant's Assessment of Arthritis Pain, Participant's Global Assessment of Arthritis Disease Activity, Physician's Global Assessment of Arthritis, CRP (mg/L) and Health Assessment Questionnaire - Disability Index (HAQ-DI).
For all visits, if any of the component scores were missing, then those scores were considered as not having met the criteria for improvement.
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Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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Percentage of Participants With Index-based ACR/EULAR Remission Rates at All Assessment Time Points
Zeitfenster: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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Index-based remission was achieved if the following requirement was met: SDAI <= 3.3.
If the SDAI value was missing at an individual assessment point, Index-based remission for that assessment was set to missing.
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Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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Percentage of Participants With Boolean-based ACR/EULAR Remission Rates at All Assessment Time Points
Zeitfenster: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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Boolean-based remission was achieved if all of the following requirements were met at the same time: TJC68 <= 1,SJC66 <= 1,CRP <= 1mg/dL, PtGA <= 10.
If one of the components was missing at an individual assessment point, Boolean-based remission for that assessment was set to missing.
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Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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Percentage of Participants in Clinical Disease Activity Index (CDAI) Remission
Zeitfenster: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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CDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician.
CDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: CDAI =TJC28 + SJC28 + GH + GP Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity and GP=physician assessment of disease activity using a 10 cm visual analogue scale with 0 = best, 100 = worst).
It ranges between 0 and 76.
High score indicates worse outcome, low score indicates better outcome.
Remission was achieved for a non-missing CDAI value <=2.8.
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Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
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Change From Baseline in SDAI at All Assessment Time Points
Zeitfenster: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
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SDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician and acute phase reactants.
The SDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal-phalangeal I-V, proximal interphalangeal I-V and knees.
It is calculated using the following formula: SDAI = TJC28 + SJC28 + GH + GP + CRP Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment, GP= physician assessment of disease activity using a 10 centimetre [cm] visual analogue scale [VAS] with 0 = best, 10 = worst), and CRP= C reactive Protein (in mg/L).
It ranges between 0.1 and 86.
High score indicates worse outcome, low score indicates better outcome.
Baseline was defined as the last available assessment prior to the start of study treatment.
Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
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Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
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Change From Baseline in CDAI at All Assessment Time Points
Zeitfenster: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
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CDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician.
CDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: CDAI =TJC28 + SJC28 + GH + GP Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity and GP=physician assessment of disease activity using a 10 cm visual analogue scale with 0 = best, 100 = worst).
It ranges between 0 and 76.
High score indicates worse outcome, low score indicates better outcome.
Baseline was defined as the last available assessment prior to the start of study treatment.
Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
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Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
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Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at All Assessment Time Points
Zeitfenster: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
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HAQ-DI is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in eight functional areas;dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities.
Each functional area contains at least two questions.
For each question, there is a four level response set that is scored from 0 (without any difficulty) to 3 (unable to do).
If aids or devices or physical assistance are used for a specific functional area and the maximum response of this functional area is 0 or 1 the according value is increased to a score of 2. HAQ-DI is only calculated if there are at least 6 functional area scores available.
The average of these non-missing functional area scores defines the continuous HAQ-DI score ranging from 0 to 3. Baseline was defined as the last available assessment prior to the start of study treatment.
Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
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Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
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Change From Baseline in Pain Score at All Assessment Time Points
Zeitfenster: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and Week 24
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Participants assessed the severity of their current arthritis pain using a 100 unit visual analog scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain.
Baseline was defined as the last available assessment prior to the start of study treatment.
Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
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Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and Week 24
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Change From Baseline in Physical and Mental Component Scores (PCS, MCS) and in Domain Scores of Short Form 36 (SF-36) at All Assessment Time Points
Zeitfenster: Baseline and Weeks 4, 12, 24
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SF-36 is a generic health survey containing 36 questions covering 8 domains of health.
SF-36 yields an 8-scale profile of functional health and well-being scores as well as PCS and MCS health summary scores.
The version 2, 1-week recall questionnaire was used.
Recoding, calculations and standardization were done as per the User's manual of SF-36.
Domain scores were only calculated if less than half of the item scores were missing.
All raw domain scores were transformed on a 0-100 scale (transformed domain scores) and then standardized into norm-based scores using Z-score.
Following the transformation of the 8 domain scores into z-scores, the MCS and PCS were aggregated (AGG) using weights as PCS/MCS = 50 + (AGG_PHYS *10/AGG_MENT *10).
High score (worse outcome) and low score (better outcome).
Baseline was defined as the last available assessment prior to the start of study treatment.
Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
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Baseline and Weeks 4, 12, 24
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Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at All Assessment Time Points
Zeitfenster: Baseline and Weeks 4, 12, 24
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The FACIT-fatigue questionnaire is a participant reported measure developed to assess fatigue consisting of 13 statements regarding feeling fatigue using a numeric rating scale ranging from 0 to 4. For only two of the items (i.e.
Answer 5 [An5] and An7) a higher value represents a lower fatigue; 11 of the item scores (i.e.
HI7, HI12, An1, An2, An3, An4, An8, An12, An14, An15, An16) have to be reversed by subtracting the captured value from 4 (0 is turned to a 4; 1 into 3; 3 into 1; 4 into 0).
After performing the reversals the sum of the non-missing individual items were multiplied by 13 and divided by the number of the non-missing individual items.
The final score ranges from 0 to 52 with higher values representing a lower fatigue (i.e. a better quality of life).
Baseline was defined as the last available assessment prior to the start of study treatment.
Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
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Baseline and Weeks 4, 12, 24
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Change From Baseline in Brief Fatigue Inventory (BFI) Question 3 at All Assessment Time Points
Zeitfenster: Baseline and Weeks 4, 12, 24
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BFI is a self-reported instrument consisting of nine questions which correlate well with quality-of-life measures.
For this study, Question 3 only was used which asked about fatigue severity at its worst in the last 24 hours.
A discrete 11 unit numeric reporting scale was used where 0 =No fatigue, and 10=As bad as you can imagine.
Baseline was defined as the last available assessment prior to the start of study treatment.
Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
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Baseline and Weeks 4, 12, 24
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Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Zeitfenster: Up to 62 weeks
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An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situations as per Medical or Scientific judgment.
Overall AEs and SAEs for the entire study duration until follow-up have been presented.
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Up to 62 weeks
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Number of Participants With Serious Infections
Zeitfenster: Up to 62 weeks
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An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Serious infections were categorized as AE of special interest.
The number of participants with overall serious infections have been presented.
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Up to 62 weeks
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Number of Participants With Opportunistic Infections
Zeitfenster: Up to 62 weeks
|
An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Opportunistic infections were categorized as AE of special interest.
The number of participants with overall opportunistic infections have been presented.
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Up to 62 weeks
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Number of Participants With Pulmonary Events
Zeitfenster: Up to 62 weeks
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Pulmonary assessments were performed to determine the number of participants with pulmonary events including persistent cough, persistent dyspnea, and persistent Diffusing capacity of the lung for carbon monoxide (DLCO).
Persistent is defined as any event with duration >=15 days.
Baseline was defined as the last available assessment prior to the start of study treatment.
The number of participants experiencing pulmonary events have been reported.
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Up to 62 weeks
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Number of Participants With Worst-case Post-Baseline Results for Pulse Oximetry
Zeitfenster: Up to 62 weeks
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Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body.
Oxygen binds to hemoglobin in red blood cells when moving through the lungs.
A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen, that is called as blood oxygen saturation.
Baseline was defined as the last available assessment prior to the start of study treatment.
The number of participants with blood oxygen level < 80%, 80% to <90% and >=90% have been reported.
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Up to 62 weeks
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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Allgemeine Veröffentlichungen
- C Buckley, J Simon Campos, V Zhdan, K Davy, D Inman, E Fisheleva, A Gupta, M Layton, N Mitchell, J Patel, R Williamson, D Saurigny, P-P Tak, C Hawkes, B Becker. A Phase IIb Dose-Ranging Randomised Study of Efficacy, Patient-Reported Outcomes and Safety of the Anti-Granulocyte Macrophage Colony-Stimulating Factor Antibody Otilimab (GSK3196165) in Patients with Rheumatoid Arthritis. Lancet Rheumatol. 2020; DOI: 10.1016/S2665-9913(20)30229-0
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
23. Juli 2015
Primärer Abschluss (Tatsächlich)
22. Dezember 2017
Studienabschluss (Tatsächlich)
29. Dezember 2017
Studienanmeldedaten
Zuerst eingereicht
20. Juli 2015
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
20. Juli 2015
Zuerst gepostet (Schätzen)
22. Juli 2015
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
11. Januar 2021
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
10. Dezember 2020
Zuletzt verifiziert
1. Dezember 2020
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 201755
- 2014-003453-34 (EudraCT-Nummer)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Ja
Beschreibung des IPD-Plans
IPD for this study is available via the Clinical Study Data Request site.
IPD-Sharing-Zeitrahmen
IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
IPD-Sharing-Zugriffskriterien
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place.
Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Art der unterstützenden IPD-Freigabeinformationen
- Studienprotokoll
- Statistischer Analyseplan (SAP)
- Einwilligungserklärung (ICF)
- Klinischer Studienbericht (CSR)
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Nein
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Nein
Produkt, das in den USA hergestellt und aus den USA exportiert wird
Nein
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .