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

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ClinicalTrials.gov Identifier: NCT02683785
Recruitment Status : Completed
First Posted : February 17, 2016
Results First Posted : December 14, 2018
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE January 21, 2016
First Posted Date  ICMJE February 17, 2016
Results First Submitted Date  ICMJE November 26, 2018
Results First Posted Date  ICMJE December 14, 2018
Last Update Posted Date April 10, 2019
Actual Study Start Date  ICMJE March 17, 2016
Actual Primary Completion Date November 29, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
Change From Baseline in 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6 [ Time Frame: Baseline (Day 1 Pre-dose) and 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).
Original Primary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
Change from baseline in 24-hour average hand pain intensity at Week 6 [ Time Frame: Baseline and Week 6 ]
Measured by daily pain Numerical Rating Scale (NRS) averaged over the 7 days prior to assessment visit.
Change History Complete list of historical versions of study NCT02683785 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2019)
  • Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit [ Time Frame: Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12 ]
    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 is calculated by 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.
  • Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit [ Time Frame: Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12 ]
    Participants were required to complete a daily pain NRS based on their 24-hour worst 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 score is calculated as sum of daily 24 hours worst 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.
  • Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit [ Time Frame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22) ]
    Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 30 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is reported.
  • Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit [ Time Frame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22) ]
    Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 50 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.
  • Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit [ Time Frame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22) ]
    Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 30 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.
  • Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit [ Time Frame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22) ]
    Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 50 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.
  • Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. [ Time Frame: Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12 ]
    The AUSCAN Index is a self-administered questionnaire consisting of a 15-item scale which measures pain (5 items), stiffness (1 item) and degree of disability/physical function (9 items) during the preceding 48 hours. All items are rated on NRS scale with anchors "0" (none) to "10" (extreme). The scores for the pain and physical function components were calculated as simple summation of the item scores relating to that domain, so the Pain component ranges from 0 (i.e. all pain item scores are scored 0 [none]) to 50 (i.e. all pain item scores are scored 10 [extreme]), and the Physical Function component ranges from 0 (i.e. all physical function item scores are scored 0 [none]) to 90 (i.e. all physical function item scores are scored 10 [extreme]). The total AUSCAN score was calculated as simple summation of the 15 item scores and therefore ranges from 0 to 150. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
  • Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit [ Time Frame: Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12 ]
    Swollen Hand Joint Count was measured by the total number of soft tissue swollen hand joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joint across both hands. In case of missing observations for soft tissue swollen hand joints then the remaining observations were assessed and weighted by dividing the number presented by the number of non-missing, and by multiplying by 30 for the joint count. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
  • Change From Baseline in Number of Tender Hand Joints at Each Visit [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 10, and 12 ]
    Tender Hand Joint Count was measured by the total number of tender joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joints across both hands. A joint was considered tender if it was scored >0 on the tender joint severity scale. Joints were rated 0=no pain/tenderness, 1=mild pain, 2=moderate pain and 3=severe pain. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
  • Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity [ Time Frame: Baseline (Day 1 Pre-dose), Weeks 2, 4, 8, and 12 ]
    Physicians were required to complete the global assessment of disease activity using single PhGA item with a NRS ranging from 0 (none) to 10 (extremely active). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
  • Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity [ Time Frame: Baseline, Weeks 2, 4, 8, and 12 ]
    Participants were required to complete the global assessment of disease activity using single PtGA item with an NRS ranging from 0 (very well) to 10 (very poor). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
  • Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: Up to Week 22 ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who received at least one dose of study treatment (GSK3196165 or placebo) were included in Safety Population.
  • Number of Participants With Infections [ Time Frame: Up to Week 22 ]
    Adverse events of special interest (AESI) included serious infections like serious respiratory infections and tuberculosis and other opportunistic infections. Number of participants with infections has been reported.
  • Number of Participants With Pulmonary Events [ Time Frame: Up to Week 22 ]
    Pulmonary events like pulmonary alveolar proteinosis (PAP), persistent (for 3 consecutive weeks) reduction in diffusing capacity of the lungs for carbon monoxide (DLCO) > 15 percentage, persistent (for 3 consecutive weeks) cough and/or dyspnea and non- life threatening pulmonary changes related to surfactant accumulation is presented.
  • Number of Participants With Anti-GSK3196165 Binding Antibodies [ Time Frame: Up to Week 22 ]
    Serum samples were collected at indicated time points for anti-drug antibody (ADA) measurements. Anti-GSK3196165 binding antibody detection assay using tiered testing schema: screening, confirmation and titration steps was used for immunogenicity analysis. Samples taken after dosing with GSK3196165 that have a value at or above the cut-point were considered treatment-emergent ADA-positive. The number of participants with change from Baseline to any time post Baseline in the results of immunogenicity assessment as indicated by: negative to positive, positive to positive, positive to negative and negative to negative are presented.
  • Apparent Clearance After Subcutaneous Administration (CL/F) of GSK3196165 [ Time Frame: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22 ]
    Blood samples were collected at indicated time points and CL/F was estimated using population PK analysis. Participants in the 'Safety' population who have at least one valid PK assessment were included Pharmacokinetic (PK) Population.
  • Apparent Steady State Volume of Distribution After Subcutaneous Administration (Vss/F) of GSK3196165 [ Time Frame: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22 ]
    Blood samples were collected at indicated time points and Vss/F was estimated using population PK analysis.
  • Absoption Rate Constant (Ka) of GSK3196165 [ Time Frame: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22 ]
    Blood samples were collected at indicated time points and Ka was estimated using population PK analysis.
  • Serum Concentration of GSK3196165 by Visit [ Time Frame: Pre-dose on Day 3, Weeks 1, 4, 6, 12, follow up (Week 22) ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
  • Change from baseline in 24-hour average and worst hand pain intensity at each visit [ Time Frame: Baseline through follow-up (Day 155) ]
    Measured by daily pain Numerical Rating Scale (NRS) and averaged over the 7 days prior to each assessment visit.
  • Proportion of subjects in each treatment group achieving a 30% or 50% reduction in 24-hour average or worst hand pain intensity at each visit [ Time Frame: Baseline through follow-up (Day 155) ]
    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 [ Time Frame: Baseline through Day 85 ]
    AUSCAN total and domains (pain, morning stiffness, function) scores at each visit will be assessed.
  • Change in number of swollen and tender hand joints at each visit [ Time Frame: Baseline through follow-up (Day 155) ]
  • Change from baseline in patient global assessment (PtGA) and physician global assessment (PhGA) of disease activity [ Time Frame: Baseline through follow-up (Day 155) ]
    Patient global assessment will be completed by the subject, the physician global assessment will be completed by the clinician. Both measures are single Numerical Rating Scale (NRS) questions administered via an electronic device.
  • Incidence of adverse events and serious adverse events, including infections and pulmonary events [ Time Frame: Baseline through follow-up (Day 155) ]
  • Anti-GSK3196165 antibodies [ Time Frame: Baseline through Day 85 ]
    Serum samples will be tested, as a measure of immunogenicity.
  • Population pharmacokinetics - total body clearance from plasms [ Time Frame: Day 1 through Day 43 ]
    Total body clearance from plasma (CL/F)
  • Population pharmacokinetics - total volume distribution [ Time Frame: Day 1 through Day 43 ]
    Total volume of distribution (Vss/F)
  • Population pharmacokinetics - absorption rate constant [ Time Frame: Day 1 through Day 43 ]
    Absorption rate constant (Ka)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Investigate the Efficacy and Safety of GSK3196165 in Inflammatory Hand Osteoarthritis
Official Title  ICMJE A Multi-centre Phase IIa Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of GSK3196165 in Subjects With Inflammatory Hand Osteoarthritis
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Osteoarthritis
Intervention  ICMJE
  • Drug: 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.
  • Drug: Placebo
    Matching placebo will be administered as above.
Study Arms  ICMJE
  • Experimental: GSK3196165
    Subjects will receive a total of 8 doses of GSK3196165 over a 12-week treatment period.
    Intervention: Drug: GSK3196165
  • Placebo Comparator: Placebo
    Subjects will receive a total of 8 doses of placebo over a 12-week treatment period.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 12, 2017)
44
Original Estimated Enrollment  ICMJE
 (submitted: February 11, 2016)
40
Actual Study Completion Date  ICMJE November 29, 2017
Actual Primary Completion Date November 29, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Netherlands,   Poland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02683785
Other Study ID Numbers  ICMJE 204851
2015-003089-96 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP