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

NCT02683785 | Completed Phase 2 Results

• 2 other identifiers: 2048512015-003089-96
• Study Type: interventional
• Target: 44
• Locations: 5 countries
• Sites: 16

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

Keywords

Pain intensity; Hand Osteoarthritis; GSK3196165; AUSCAN; GM-CSF; Numerical Rating Scale

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6

  Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors "0" (no pain) and "10" (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score was calculated as sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. Intent-To-Treat Population comprised of all randomized participants who received at least one dose of study treatment (GSK3196165 or placebo).

  Baseline (Day 1 Pre-dose) and Week 6

Secondary Outcomes (19)

• Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit

  Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

• Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit

  Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

• Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit

  Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

• Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit

  Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

• Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit

  Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

Study Arms (2)

GSK3196165

EXPERIMENTAL

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

Drug: GSK3196165

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

GSK3196165 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.

GSK3196165

Placebo DRUG

Matching placebo will be administered as above.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (16)

GSK Investigational Site

Miami, Florida, 33015, United States

Location

GSK Investigational Site

Duncansville, Pennsylvania, 16635, United States

Location

GSK Investigational Site

Erlangen, Bavaria, 91054, Germany

Location

GSK Investigational Site

Fulda, Hesse, 36043, Germany

Location

GSK Investigational Site

Rendsburg, Schleswig-Holstein, 24768, Germany

Location

GSK Investigational Site

Enschede, 7511JX, Netherlands

Location

GSK Investigational Site

Rotterdam, 3015 CE, Netherlands

Location

GSK Investigational Site

Sneek, 8601 ZK, Netherlands

Location

GSK Investigational Site

Bialystok, 15-879, Poland

Location

GSK Investigational Site

Nowa Sól, 67-100, Poland

Location

GSK Investigational Site

Warsaw, 00-660, Poland

Location

GSK Investigational Site

Warsaw, 03-291, Poland

Location

GSK Investigational Site

Canterbury, Kent, CT1 3NG, United Kingdom

Location

GSK Investigational Site

Derby, DE22 3NE, United Kingdom

Location

GSK Investigational Site

North Shields, NE298NH, United Kingdom

Location

GSK Investigational Site

York, YO31 8HE, United Kingdom

Location

Related Publications (2)

• 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

  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.

  PMID: 38273625 DERIVED

MeSH Terms

Conditions

Osteoarthritis; Pain

Interventions

Otilimab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2016
• First Posted: February 17, 2016
• Study Start: March 17, 2016
• Primary Completion: November 29, 2017
• Study Completion: November 29, 2017
• Last Updated: January 11, 2021
• Results First Posted: December 14, 2018

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
• Access Criteria: 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.

Locations

PL (4); DE (3); US (2); GB (4); NL (3)