Mechanistic Study of GSK3196165 Plus Methotrexate (MTX) in Subjects With Active Rheumatoid Arthritis

NCT ID: NCT02799472

Last Updated: 2021-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-15
• Study Completion Date: 2017-10-30

Brief Summary

This study is designed to explore the activity of granulocyte-macrophage colony stimulating factor (GM-CSF) signaling pathway in subjects with rheumatoid arthritis (RA), the potential impact of inhibition of this axis by GSK3196165, and to evaluate whether there are any differences in the GM-CSF axis between subjects with early RA compared with those with more established disease. This study also aims to establish the potential impact of GSK3196165 on inflammatory structural joint damage in the hand/wrist using magnetic resonance imaging (MRI). This is a randomized Phase IIa, multi-center, double-blind, placebo-controlled parallel group study. Approximately 40 subjects with active RA despite treatment with disease-modifying antirheumatic drugs (DMARDs) (including conventional or biologic) will be randomized into the study, following a screening period of up to 6 weeks. The total treatment period is up to 10 weeks, with a 12-week follow-up period after the last dose (Week 22).

Conditions

Arthritis, Rheumatoid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GSK3196165 + MTX arm

Subjects will receive GSK3196165 (initially weekly, then every other week) in combination with MTX (15-25 mg/week) and folic (or folinic) acid (\>=5 mg/week).

Group Type: EXPERIMENTAL

GSK3196165

Intervention Type: DRUG

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

MTX

Intervention Type: DRUG

Capsule, tablet or liquid administered orally or as SC injection.

Folic (or folinic) acid

Intervention Type: DRUG

Capsule, tablet or liquid and will be administered orally.

Placebo + MTX arm

Subjects will receive placebo (initially weekly, then every other week) in combination with MTX (15-25 mg/week) and folic (or folinic) acid (\>=5 mg/week).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0.9% weight by volume (w/v) sodium chloride solution administered as SC injection.

MTX

Intervention Type: DRUG

Capsule, tablet or liquid administered orally or as SC injection.

Folic (or folinic) acid

Intervention Type: DRUG

Capsule, tablet or liquid and will be administered orally.

Interventions

GSK3196165

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

Intervention Type: DRUG

Placebo

0.9% weight by volume (w/v) sodium chloride solution administered as SC injection.

Intervention Type: DRUG

MTX

Capsule, tablet or liquid administered orally or as SC injection.

Intervention Type: DRUG

Folic (or folinic) acid

Capsule, tablet or liquid and will be administered orally.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age >=18 years at the time of signing informed consent.
• Meets American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 RA Classification Criteria AND subject not diagnosed before age of 16 years.
• Functional class I, II or III defined by the 1992 ACR Classification of Functional Status in RA.
• Active disease as defined by:

• Swollen joint count of >=4 (66-joint count) and tender joint count of >=4 (68-joint count) at screening and Day 1.

AND • Disease activity score for 28 different joints with C-reactive protein (CRP) value (DAS28[CRP]) >=3.2 at screening.

AND

• CRP >=3.0 milligrams (mg)/liter (L).

• Signs of inflammation such as synovitis in the MRI scan of the most-affected hand.
• Must be currently taking MTX (15-25 mg weekly) (oral/injected) 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, example (e.g.) hepatic or hematologic toxicity, or per local requirement.
• Body weight >=45 kilograms (kg).
• Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria.
• Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
• Willing to continue or initiate treatment with oral folic acid (at least 5 mg/week) or equivalent and be treated during the entire study (mandatory co-medication for MTX treatment).
• 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, or women planning to become pregnant or initiating breastfeeding.
• History of other inflammatory rheumatologic 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 (in the opinion of the investigator) persistent cough or clinically significant or unstable 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.
• Contraindication to MRI scanning.
• Current/previous Hepatitis B virus (HBV), Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) 1 or 2 infection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

El Cajon, California, United States

GSK Investigational Site

Fort Lauderdale, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Pinellas Park, Florida, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Duncansville, Pennsylvania, United States

GSK Investigational Site

Memphis, Tennessee, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, Germany

GSK Investigational Site

Püttlingen, , Germany

GSK Investigational Site

Elblag, , Poland

GSK Investigational Site

Nowa Sól, , Poland

GSK Investigational Site

Piaseczno, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Wroclaw, , Poland

Countries

United States; Germany; Poland

References

Genovese MC, Berkowitz M, Conaghan PG, Peterfy C, Davy K, Fisheleva E, Gupta A, Inman D, Janiczek R, Layton M, Mitchell N, Patel J, Roberts A, Saurigny D, Smith JE, Williamson R, Tak PP. MRI of the joint and evaluation of the granulocyte-macrophage colony-stimulating factor-CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic study. Lancet Rheumatol. 2020 Nov;2(11):e666-e676. doi: 10.1016/S2665-9913(20)30224-1. Epub 2020 Oct 7.

Reference Type: BACKGROUND

PMID: 38279363 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-004386-91

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205180

Identifier Type: -

Identifier Source: org_study_id