Clinical trial NCT02683785: A Study to Investigate the Efficacy and Safety of GSK3196165 in Inflammatory Hand Osteoarthritis
Official title: A Multi-centre Phase IIa Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of GSK3196165 in Subjects With Inflammatory Hand Osteoarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis
Keywords: Pain intensity
Hand Osteoarthritis
GSK3196165
AUSCAN
GM-CSF
Numerical Rating Scale
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-02-17
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change From Baseline in 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6
timeFrame: Baseline (Day 1 Pre-dose) and Week 6
Secondary outcomes:
measure: Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
timeFrame: Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
measure: Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
timeFrame: Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
measure: Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
timeFrame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
measure: Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
timeFrame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
measure: Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
timeFrame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
measure: Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
timeFrame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
measure: Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
timeFrame: Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12
measure: Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
timeFrame: Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12
measure: Change From Baseline in Number of Tender Hand Joints at Each Visit
timeFrame: Baseline, Weeks 1, 2, 4, 6, 8, 10, and 12
measure: Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity
timeFrame: Baseline (Day 1 Pre-dose), Weeks 2, 4, 8, and 12
measure: Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to Week 22
measure: Number of Participants With Infections
timeFrame: Up to Week 22
measure: Number of Participants With Pulmonary Events
timeFrame: Up to Week 22
measure: Number of Participants With Anti-GSK3196165 Binding Antibodies
timeFrame: Up to Week 22
measure: Apparent Clearance After Subcutaneous Administration (CL/F) of GSK3196165
timeFrame: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22
measure: Apparent Steady State Volume of Distribution After Subcutaneous Administration (Vss/F) of GSK3196165
timeFrame: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22
measure: Absoption Rate Constant (Ka) of GSK3196165
timeFrame: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22
measure: Serum Concentration of GSK3196165 by Visit
timeFrame: Pre-dose on Day 3, Weeks 1, 4, 6, 12, follow up (Week 22)
Other outcomes:
Locations:
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Duncansville
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Erlangen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Fulda
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Rendsburg
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Sneek
country: Netherlands
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Nowa Sol
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Canterbury
country: United Kingdom
facility: GSK Investigational Site
state: Kent
city: Derby
country: United Kingdom
facility: GSK Investigational Site
city: North Shields
country: United Kingdom
facility: GSK Investigational Site
city: York
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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