Clinical trial NCT02504671: Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Keywords: DMARD-IR
GSK3196165
Rheumatoid Arthritis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-07-22
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline in DAS28(CRP) at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Who Achieved DAS28(CRP) Remission (DAS28 <2.6) at All Time Points
timeFrame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
measure: Change From Baseline in DAS28(CRP) at All Assessment Time Points
timeFrame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
measure: Time to First DAS28(CRP) Remission
timeFrame: Up to Week 62
measure: Percentage of Participants Achieving Categorical DAS28(CRP) Response (Moderate/Good [European League Against Rheumatism] EULAR Response) at All Assessment Time Points
timeFrame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
measure: Percentage of Participants With American College of Rheumatology's (ACR) 20/50/70 Response Rates at All Assessment Time Points
timeFrame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
measure: Percentage of Participants With Index-based ACR/EULAR Remission Rates at All Assessment Time Points
timeFrame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
measure: Percentage of Participants With Boolean-based ACR/EULAR Remission Rates at All Assessment Time Points
timeFrame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
measure: Percentage of Participants in Clinical Disease Activity Index (CDAI) Remission
timeFrame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)
measure: Change From Baseline in SDAI at All Assessment Time Points
timeFrame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
measure: Change From Baseline in CDAI at All Assessment Time Points
timeFrame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
measure: Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at All Assessment Time Points
timeFrame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24
measure: Change From Baseline in Pain Score at All Assessment Time Points
timeFrame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and Week 24
measure: 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
timeFrame: Baseline and Weeks 4, 12, 24
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at All Assessment Time Points
timeFrame: Baseline and Weeks 4, 12, 24
measure: Change From Baseline in Brief Fatigue Inventory (BFI) Question 3 at All Assessment Time Points
timeFrame: Baseline and Weeks 4, 12, 24
measure: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
timeFrame: Up to 62 weeks
measure: Number of Participants With Serious Infections
timeFrame: Up to 62 weeks
measure: Number of Participants With Opportunistic Infections
timeFrame: Up to 62 weeks
measure: Number of Participants With Pulmonary Events
timeFrame: Up to 62 weeks
measure: Number of Participants With Worst-case Post-Baseline Results for Pulse Oximetry
timeFrame: Up to 62 weeks
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: GSK Investigational Site
city: Plovdiv
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Barrie
country: Canada
facility: GSK Investigational Site
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Bruntal
country: Czechia
facility: GSK Investigational Site
city: Praha 5
country: Czechia
facility: GSK Investigational Site
city: Praha
country: Czechia
facility: GSK Investigational Site
city: Uherske Hradiste
country: Czechia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Bad Doberan
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Kistarcsa
country: Hungary
facility: GSK Investigational Site
city: Veszprém
country: Hungary
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Bologna
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Cuernavaca
country: Mexico
facility: GSK Investigational Site
state: Morelos
city: Cuernavaca
country: Mexico
facility: GSK Investigational Site
state: Morelos
city: Merida
country: Mexico
facility: GSK Investigational Site
state: Yucatán
city: San Luis Potosí
country: Mexico
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Bytom
country: Poland
facility: GSK Investigational Site
city: Grodzisk Mazowiecki
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Torun
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Novosibirsk
country: Russian Federation
facility: GSK Investigational Site
city: Omsk
country: Russian Federation
facility: GSK Investigational Site
city: Ryazan
country: Russian Federation
facility: GSK Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Tver
country: Russian Federation
facility: GSK Investigational Site
city: Vladimir
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Pretoria
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Panorama / Cape Town
country: South Africa
facility: GSK Investigational Site
city: Stellenbosch
country: South Africa
facility: GSK Investigational Site
city: Coruña
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Ivano-Frankivsk
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kryvyi Rih
country: Ukraine
facility: GSK Investigational Site
city: Lviv
country: Ukraine
facility: GSK Investigational Site
city: Odesa
country: Ukraine
facility: GSK Investigational Site
city: Poltava
country: Ukraine
facility: GSK Investigational Site
city: Sumy
country: Ukraine
facility: GSK Investigational Site
city: Vinnytsia
country: Ukraine
facility: GSK Investigational Site
city: Vinnytsya
country: Ukraine
facility: GSK Investigational Site
city: Zhytomyr
country: Ukraine
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Leeds
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Buckley CD, Simon-Campos JA, Zhdan V, Becker B, Davy K, Fisheleva E, Gupta A, Hawkes C, Inman D, Layton M, Mitchell N, Patel J, Saurigny D, Williamson R, Tak PP. Efficacy, patient-reported outcomes, and safety of the anti-granulocyte macrophage colony-stimulating factor antibody otilimab (GSK3196165) in patients with rheumatoid arthritis: a randomised, phase 2b, dose-ranging study. Lancet Rheumatol. 2020 Nov;2(11):e677-e688. doi: 10.1016/S2665-9913(20)30229-0. Epub 2020 Oct 7.