A Study to Investigate the Efficacy and Safety of GSK3196165 in Inflammatory Hand Osteoarthritis
Condition: Osteoarthritis
MeSH terms: Osteoarthritis
Intervention: GSK3196165; Placebo
Intervention description: 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.; Matching placebo will be administered as above.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pain intensity; Hand Osteoarthritis; GSK3196165; AUSCAN; GM-CSF; Numerical Rating Scale

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.
    

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.