Inflammatory Hand Osteoarthritis MedDRA version: 19.1 Level: LLT Classification code 10019115 Term: Hand osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Code: GSK3196165
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
CAS Number: 1638332-55-4
Current Sponsor c
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: AGE 1. Age = 18 years at the time of signing the informed consent. TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY 2. Meets ACR classification of OA and is intolerant to, or has not responded to analgesics (level 1 and 2) or to NSAIDs for at least 10 days in the past 3 months. 3. Must have active disease with at least two swollen and tender PIP and/or DIP joints in the affected hand*. 4. Signs of inflammation such as synovitis in the MRI scan of the affected hand*. 5. Must have a patient’s self assessment of 24h average hand pain intensity of at least ‘5’ on an 11-point NRS (0-10), calculated as an average using data from the 7 days prior to assessment date. *If only one hand is affected by HOA and meets the inclusion criteria, the affected hand will be documented at screening and used for all assessments. In cases where both hands are affected by HOA and both meet the inclusion criteria, then the dominant hand will be documented at screening and this hand will be used for the MRI assessments throughout the study. WEIGHT 6. Body weight = 45 kg. SEX 7. Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria detailed in Appendix 5. INFORMED CONSENT 8. Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications. OTHER SAFETY-RELATED 9. Diffusing capacity of the lung for carbon monoxide (DLCO) = 70 % predicted and forced expiratory volume in 1 second (FEV1) = 80 % predicted. 10. No evidence of active or latent infection with Mycobacterium tuberculosis (TB), as defined by all of the following: a. No history of active or latent TB infection irrespective of treatment status. b. A negative diagnostic TB test within 28 days of baseline (Day 1) defined as: a negative QuantiFERON Gold test or T-spot test (may be performed locally) (NB: 2 successive indeterminate QuantiFERON tests will be considered as a positive result). Note: If there has been recent close contact with persons who have active TB prior to study enrolment the subject will be referred to a TB physician to undergo additional evaluation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER FUNCTION AND QTc INTERVAL) 1. Pregnant or lactating females. 2. Significant unstable or uncontrolled acute or chronic disease please view protocol for further information. 3. History of any clinically significant inflammatory disease other than inflammatory HOA, especially, but not limited to, rheumatoid arthritis or spondylarthropathies. 4. Diagnosis of rheumatoid arthritis, fibromyalgia, gout, calcium pyrophosphate deposition disease CPPD, pseudogout,hemochromatosis or other inflammatory rheumatological or autoimmune disorders. 5. Clinical suspicion of, or previous investigation for CPPD or pseudogout, or history of chondrocalcinosis. 6. Any injury, medical or surgical procedure to the affected joint(s) that may interfere with evaluation of the target HOA joint(s). 7. History of any clinically-significant respiratory disease that required treatment and/or follow up under the direction of a physician or any respiratory disease. Please view protocol for further information. 8. Clinically-significant or unstable (in the opinion of the Investigator) persistent cough or dyspnea that is unexplained. 9. QTc > 450 msec or QTc > 480 msec in subjects with Bundle Branch Block based on averaged values of triplicate electrocardiograms obtained over a brief (e.g. 5-10 minute) recording period -The QTc is the QT interval corrected for heart rate according to Bazett’s formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machine read or manually over-read. 10. ALT >2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 1.5xULN within 28 days of Day 1. 14. Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency. 15. 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. 16. Active infections, or history of recurrent infections (excluding recurrent fungal infections of the nail bed), or have required management of acute or chronic infections, please view protocol for further information. 17. A vaccination (live or attenuated) within 30 days of Day 1 or BCG vaccination within 365 days of Day 1, or a live vaccination planned during the course of the study. 18. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy potential of GSK3196165 on pain in inflammatory HOA. ;Primary end point(s): Change from baseline in 24h average hand pain intensity.;Timepoint(s) of evaluation of this end point: Week 6.; Secondary Objective: - To evaluate impact of GSK3196165 on average and worst HOA pain, over time. - To assess the impact of GSK3196165 on hand pain (on use), stiffness and function, over time. - To assess the impact of GSK3196165 on HOA inflammation. -To assess potential impact of GSK3196165 on disease activity in HOA. - To assess safety of GSK3196165 in HOA patients, over the study duration. -To assess population pharmacokinetics of GSK3196165 in HOA. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Pain (Week 6, 12, 22), hand function (Week 0, 1, 2, 4, 6, 8, 10, 12) safety (throughout the study), pharmacokinetics (Day 0, 3, 8, 29 and 43,85,155), inflammation (Week 0, 1, 2, 4, 6, 8, 10, 12, 22) and disease activity (Week 0, 2) ; Secondary end point(s): Change from baseline in 24h average hand pain intensity at each visit, measured by daily pain NRS and averaged over the 7 days prior to each assessment visit. • Change from baseline of worst hand pain intensity over 24h at each visit, measured by daily NRS and averaged over the 7 days prior to each assessment visit. • Proportion of subjects in each treatment group achieving a 30% reduction in 24h average hand pain intensity at each visit, measured by daily NRS averaged over the 7 days prior to assessment visit. • Proportion of subjects in each treatment group achieving a 50% reduction in 24h average hand pain intensity at each visit, measured by daily NRS averaged over the 7 days prior to assessment visit. • Proportion of subjects in each treatment group achieving a 30% reduction in 24h worst hand pain intensity at each visit, measured by daily NRS averaged over the 7 days prior to assessment visit. • Proportion of subjects in each treatment group achieving a 50% reduction in 24h worst hand pain intensity at each visit, measured by daily NRS averaged over the 7 days prior to assessment visit. • Change from baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS, total and domains (pain, morning stiffness, function) scores at each visit. • Change in number of swollen and tender hand joints at each visit. • Change from baseline in patient global assessment (PtGA) and physician global assessment (PhGA) of disease activity at Week 6 and 12 and week 22. • Incidence of adverse events | — |
Countries
Germany, Netherlands, Poland, United Kingdom, United States
Contacts
Public ContactClinical Trials HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed