A Study to Investigate the Efficacy and Safety of GSK3196165 in Inflammatory Hand Osteoarthritis

NCT ID: NCT02683785

Last Updated: 2021-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-17
• Study Completion Date: 2017-11-29

Brief Summary

This is a randomized, Phase IIa, multicentre, double-blind, placebo-controlled parallel group study with the primary objective to assess the efficacy potential of GSK3196165 on pain, in subjects with active inflammatory hand osteoarthritis (HOA).

Approximately 40 subjects will be enrolled into the study, following a screening period of up to 4 weeks. The total treatment period will be 12 weeks, with the follow up period completing at Week 22. At least 40 subjects will be randomized across the two treatment arms, to either placebo or GSK3196165 in a 1:1 ratio.

Conditions

Osteoarthritis

Study Design

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

Study Groups

GSK3196165

Subjects will receive a total of 8 doses of GSK3196165 over a 12-week treatment period.

Group Type: EXPERIMENTAL

GSK3196165

Intervention Type: DRUG

GSK3196165 will be supplied as a liquid and will be administered as a subcutaneous injection. The drug will be administered weekly for 5 injections, then every other week for 3 further injections.

Placebo

Subjects will receive a total of 8 doses of placebo over a 12-week treatment period.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo will be administered as above.

Interventions

GSK3196165

GSK3196165 will be supplied as a liquid and will be administered as a subcutaneous injection. The drug will be administered weekly for 5 injections, then every other week for 3 further injections.

Intervention Type: DRUG

Placebo

Matching placebo will be administered as above.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age >=18 years at the time of signing informed consent.
• Meets American College of Rheumatology (ACR) classification of osteoarthritis (OA) and have not responded to analgesics (level 1 and 2) or to non-steroidal anti-inflammatory drugs (NSAIDs) for at least 10 days in the past 3 months.
• Active disease at screening and randomization with at least two swollen and tender proximal interphalangeal (PIP) and/or distal interphalangeal (DIP) joints in the affected hand.
• Signs of inflammation such as synovitis in the MRI scan of the affected hand.
• Must have a subject's self assessment of 24-hour average hand pain intensity at baseline of at least '5' on an 11-point Numerical Rating Scale (NRS, 0-10).
• 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) >=70% predicted; forced expiratory volume in 1 second (FEV1) >=80% predicted.
• No evidence of active or latent infection with Mycobacterium tuberculosis (TB).

Exclusion Criteria

• Pregnant or lactating women.
• History of any clinically significant inflammatory disease other than inflammatory HOA, especially, but not limited to, rheumatoid arthritis or spondylarthropathies.
• Diagnosis of rheumatoid arthritis, fibromyalgia, gout, calcium pyrophosphate deposition disease (CPPD), pseudogout, hemochromatosis or other inflammatory rheumatological or autoimmune disorders.
• Clinical suspicion of, or previous investigation for CPPD or pseudogout, or history of chondrocalcinosis.
• Any injury, medical or surgical procedure to the affected joint(s) that may interfere with evaluation of the target HOA joint(s).
• History of infected joint prosthesis at any time, with the prosthesis still in situ. History of leg ulcers, catheters, chronic sinusitis or recurrent chest or urinary tract infections.
• Any surgical procedure, including bone or joint surgery/synovectomy within 12 weeks prior to Day 1 or any planned surgery within the duration of the study or follow-up period.
• 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.

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

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Duncansville, Pennsylvania, United States

GSK Investigational Site

Erlangen, Bavaria, Germany

GSK Investigational Site

Fulda, Hesse, Germany

GSK Investigational Site

Rendsburg, Schleswig-Holstein, Germany

GSK Investigational Site

Enschede, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

Sneek, , Netherlands

GSK Investigational Site

Bialystok, , Poland

GSK Investigational Site

Nowa Sól, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Canterbury, Kent, United Kingdom

GSK Investigational Site

Derby, , United Kingdom

GSK Investigational Site

North Shields, , United Kingdom

GSK Investigational Site

York, , United Kingdom

Countries

United States; Germany; Netherlands; Poland; United Kingdom

References

Georg Schett, Chris Bainbridge, Mario Berkowitz, Katherine Davy, Sofia Fernandes, Eduard Griep, Stephen Harrison, James Lloyd-Hughes, Alexandra Morgan-Roberts, Mark Layton, Nonna Anna Nowak, Jatin Patel, Jürgen Rech, Sarah Watts, Paul P. Tak. A Phase IIa, randomised study of the safety, pharmacokinetics, pharmacodynamics and clinical activity of the anti-GM-CSF antibody GSK3196165 in patients with hand osteoarthritis. Lancet Rheumatol. 2020; DOI: 10.1016/S2665-9913(20)30171-5

Reference Type: BACKGROUND

Schett G, Bainbridge C, Berkowitz M, Davy K, Fernandes S, Griep E, Harrison S, Gupta A, Lloyd-Hughes J, Roberts A, Layton M, Nowak NA, Patel J, Rech J, Smith JE, Watts S, Tak PP. Anti-granulocyte-macrophage colony-stimulating factor antibody otilimab in patients with hand osteoarthritis: a phase 2a randomised trial. Lancet Rheumatol. 2020 Oct;2(10):e623-e632. doi: 10.1016/S2665-9913(20)30171-5. Epub 2020 Sep 23.

Reference Type: DERIVED

PMID: 38273625 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-003089-96

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

204851

Identifier Type: -

Identifier Source: org_study_id