Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02504671
Recruitment Status : Completed
First Posted : July 22, 2015
Last Update Posted : September 17, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: GSK3196165 Drug: MTX Drug: Folic acid Drug: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 222 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : July 23, 2015
Actual Primary Completion Date : December 29, 2017
Actual Study Completion Date : December 29, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: GSK3196165
GSK3196165 is supplied as liquid and will be administered as SC injection.

Drug: MTX
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.

Drug: Folic acid
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.

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.
Drug: GSK3196165
GSK3196165 is supplied as liquid and will be administered as SC injection.

Drug: MTX
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.

Drug: Folic acid
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.

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.
Drug: GSK3196165
GSK3196165 is supplied as liquid and will be administered as SC injection.

Drug: MTX
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.

Drug: Folic acid
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.

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.
Drug: GSK3196165
GSK3196165 is supplied as liquid and will be administered as SC injection.

Drug: MTX
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.

Drug: Folic acid
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.

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.
Drug: GSK3196165
GSK3196165 is supplied as liquid and will be administered as SC injection.

Drug: MTX
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.

Drug: Folic acid
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.

Placebo Comparator: 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.
Drug: MTX
MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.

Drug: Folic acid
Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.

Drug: Placebo
Placebo is supplied as liquid as sterile 0.9% weight by volume (w/v) sodium chloride solution and will be administered as SC injection




Primary Outcome Measures :
  1. Proportion of subjects who achieve DAS28(CRP) remission [ Time Frame: Week 24 ]
    DAS28(CRP) remission is defined as a DAS28 score of <2.6 points.


Secondary Outcome Measures :
  1. Change from Baseline in DAS28 (CRP) score [ Time Frame: Baseline to Week 62 ]
    Change from Baseline in DAS28 (CRP) will be evaluated at all assessment timepoints.

  2. Disease response rates [ Time Frame: Baseline to Week 62 ]
    The proportion of subjects who achieve DAS28 (CRP) remission, ACR20/50/70, DAS28 (CRP) EULAR response will be evaluated at all assessment timepoints.

  3. Change from baseline in patient reported outcomes [ Time Frame: Baseline to Week 62 ]
    Patient reported outcomes that will be evaluated at all assessment timepoints in this study include: HAQ-DI and pain scores, and fatigue

  4. Safety and tolerability [ Time Frame: Screening to Week 62 ]
    Incidence of adverse events and serious adverse events, including infections and pulmonary events.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02504671


  Show 73 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] March 11, 2016
Statistical Analysis Plan  [PDF] August 26, 2015


Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02504671     History of Changes
Other Study ID Numbers: 201755
First Posted: July 22, 2015    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: September 2018

Keywords provided by GlaxoSmithKline:
DMARD-IR
GSK3196165
Rheumatoid Arthritis

Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Folic Acid
Vitamin B Complex
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Hematinics
Vitamins
Micronutrients
Nutrients