A Dose-Finding Study to Evaluate the Efficacy and Safety of GSK3858279 in Adults With Knee Osteoarthritis (OA) Pain
- Summary
- This is dose-finding study of GSK3858279 in participants with moderate to severe knee osteoarthritis pain. The purpose of this study is to investigate and provide the data necessary to select the optimal effective and safe dose(s) of GSK3858279.
- Acronym
- MARS-17
- Short title
- A Dose-Finding Study to Evaluate the Efficacy and Safety of GSK3858279 in Adults With Knee Osteoarthritis (OA) Pain
- Official title
- A Multicentre Randomized, Double-blind, Placebo Controlled, Dose-finding, Phase 2 Study (MARS-17) of GSK3858279 in Adult Participants With Moderate to Severe Pain Due to Knee Osteoarthritis
- Control arm
- Placebo
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Terminated
- Phase
- Phase 2
- Study type
- Interventional
- Reason stopped
- The study met futility criteria at pre-planned interim analysis, showing no clinical efficacy of the investigational drug. Based on the lack of efficacy at the interim data review, the sponsor decided to terminate the study.
- Completion date
- 2024-12-03
- First posted
- 2023-05-03
- Registry last updated
- 2025-11-10
- Primary completion date
- 2024-08-12
- Start date
- 2023-09-13
- Actual participants
- Participants
- Participant count basis
- Actual
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- GlaxoSmithKline
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT05838742
- ClinicalTrials.gov ID
- NCT05838742
- Registry record
- Open registry record
- Allocation
- Randomised
- Model
- Parallel groups
- Purpose
- Treatment
- Masking
- Double masking
- Masked roles
- Participants, Investigators
Change From Baseline in Weekly Average of Average Daily Knee Pain Intensity Using Numeric Rating Scale at Week 12
Timeframe: Baseline (Day -7 to Day -1) and at Week 12
Change from Baseline in knee pain due to Osteoarthritis were reported by weekly average of average daily pain numeric rating scale (NRS) at Week 12. The pain NRS is an 11-point scale (ranging from 0-10) for self-reporting of average daily knee pain where 0 indicates no pain, and 10 indicates the worst possible pain. For each participant, the weekly average of average daily pain score was calculated using the mean value of available daily pain scores falling in the assessment window for each week. A negative change from baseline indicates an improvement in pain. Participants were asked to complete the pain NRS questionnaire at the same time in the evening each day. Baseline scores were assigned based on an average of 7 days prior to day 1 dosing visit. Posterior mean change from baseline, 95 percent (%) credible interval (CI) was derived using Bayesian mixed model repeated measures. The data presented are the posterior mean with 95% confidence interval refers to 95% credible interval.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score At Week 12
Timeframe: Baseline (Day 1) and at Week 12
The WOMAC pain subscale have a recall period of 48 hours and includes 5 subscales of pain assessment: 1-walking on flat, 2-going up downstairs, 3-at night while in bed, 4-sitting or lying; 5-standing upright. The total WOMAC pain subscale score ranges from 0-10; where 0 is no pain and 10 is extreme pain. The WOMAC pain subscale score was calculated by taking average of the 5 pain subscales at each visit. Change from baseline was calculated for each visit as the mean WOMAC Pain subscale score minus the mean baseline WOMAC Pain subscale score. A negative change from baseline indicates an improvement in pain. Baseline WOMAC scores for each participant were assigned based on the score measured prior to first dosing on Day1 visit. Posterior mean change from baseline, 95 percent (%) credible interval (CI) was derived using Bayesian mixed model repeated measures. The data presented are the posterior mean change from baseline with a 95% confidence interval refers to 95% Credible Interval.
Change From Baseline in WOMAC Physical Function Subscale Score at Week 12
Timeframe: Baseline (Day 1) and at Week 12
The WOMAC function subscale have a recall period of 48 hours and include 17 items of daily function assessments. The total WOMAC physical function subscale score ranges from 0-10 scale; where 0 is no difficulty and 10 is extremely difficult. The WOMAC physical function subscale score was calculated by taking the average of the 17 physical function subscales at each visit. Change from baseline was calculated for each visit as the mean WOMAC function subscale score minus the mean baseline WOMAC function subscale score. Baseline scores for each participant were assigned based on the score measured prior to first dosing on Day1 visit. A negative change from baseline indicated improvement. Posterior mean change from baseline, 95 percent (%) credible interval (CI) was derived using Bayesian mixed model repeated measures. The data presented are the posterior mean change from baseline with a 95% confidence interval refers to 95% Credible Interval.
Change From Baseline in Patient Global Assessment Of Disease (PtGA) at Week 12
Timeframe: Baseline (Day 1) and at Week 12
The PtGA is an assessment for disease conditions and intensity of knee osteoarthritis (OA) pain. Participants will respond on a Likert scale ranging from 1-5 based on the question "Considering all the ways in which your knee OA affects you, how do you feel your knee OA is doing today?" and to identify a number from 1 = very good (asymptomatic and no limitation to normal activities) to 5 = "very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher scores indicate worse conditions. Baseline scores for each participant were assigned based on the scores reported prior to first dosing on Day 1 visit. Posterior mean change from baseline, 95 percent (%) credible interval (CI) was derived using Bayesian mixed model repeated measures. The data presented are the posterior mean with a 95% confidence interval refers to 95% Credible Interval.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESI)
Timeframe: Up to 31 weeks
AEs, SAEs, and AESIs were collected. An AE is any untoward medical occurrence in participant, temporally associated with use of study intervention, whether or not considered related to 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, medically important were categorized as SAEs. The AESIs of the study drug included serious and opportunistic infections, tuberculosis (TB) and TB reactivation, serious hypersensitivity reactions and Injection site reactions.
Number of Participants With Greater Than or Equal to (>=) Grade 3 Hematological/Clinical Chemistry Abnormalities According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE)
Timeframe: Up to 31 weeks
The laboratory measurements included hematology and clinical chemistry. The parameters evaluated were Basophil, Eosinophil, Erythrocyte Mean Corpuscular Hemoglobin, Erythrocyte Mean Corpuscular Volume, Erythrocytes, Hematocrit, Hemoglobin, Lymphocyte, Monocyte, Neutrophils, Platelets and Reticulocytes, Alanine Aminotransferase, Albumin, Alkaline phosphatase, Aspartate Aminotransferase, Bilirubin, Calcium, Creatinine, Direct Bilirubin, Glucose, Potassium, Sodium and Urea. Worst case grade (G) increase from baseline grade was provided for all the laboratory tests that were gradable by National Cancer Institute Common Terminology Criteria (NCI CTCAE, Version 5.0). Data for any participants with the worst-case grade changes (Increase or equal to Grade 3 or Increase to Grade 4) post-baseline are reported. Missing baseline grade was assumed as grade 0.
Maximum Concentration (Cmax) of GSK3858279
Timeframe: Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12
Blood samples were collected at the indicated time points for pharmacokinetic (PK) analysis of GSK3858279 . Pharmacokinetic analysis was conducted using a model based analysis using all available data.
Time to Maximum Plasma Concentration (Tmax) of GSK3858279
Timeframe: Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12
Tmax predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.
Pre-Dose (Trough) Concentration at the End of the Dosing Interval (Ctau) of GSK3858279
Timeframe: Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12
Ctau predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.
Average Concentration Over a Dosing Interval (Cavg) of GSK3858279
Timeframe: Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12
Cavg predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.
Area Under the Time-Concentration Curve (AUC) Over the Dosing Interval (0-Tau) (AUC[0-Tau]) of GSK3858279
Timeframe: Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12
AUC(0-tau) predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 40 Years
- Maximum age
- 80 Years
- Healthy volunteers
- No
- Participant must be 40 to 80 years of age inclusive
- OA of the index knee as defined by symptomatic for ≥ 6 months with a clinical diagnosis of OA as per American College of Rheumatology (ACR) clinical diagnosis criteria.
- Kellgren and Lawrence (KL) score ≥ 2 on X-ray in the index knee
- An average of the average daily pain score of ≥4 and less than or equal to (≤) 9 by the 11-point NRS (0-10)
- Body mass index (BMI) of < 40 kilogram per meter square (kg/m^2) (inclusive).
- Capable of giving signed informed consent.
- History or presence of cardiovascular, renal, gastrointestinal, lymphatic disorders which in the opinion of the investigator would interfere with the study procedures and/or assessments.
- History or current evidence of any inflammatory arthritis such as rheumatoid arthritis, infective arthritis, Paget's disease, osteonecrosis, osteoporotic fracture, or any other joint disease that in the Investigator's opinion would interfere with the assessment of pain and other symptoms of osteoarthritis.
- History of significant trauma or surgery to a knee or hip within the last 6 months.
- Current immunodeficiency diseases including but not limited to acquired immunodeficiency disorder or immunoglobulin deficiency.
- Current or previous active Mycobacterium tuberculosis
- History or evidence of clinically significant multiple or severe drug allergies
- History of malignancy within the last 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35 percent (%)
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- Evidence of renal insufficiency, indicated by estimated creatinine clearance < 60 milliliter/ minute (mL/min)/1.73 square meter (m^2) at screening.
- Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
- GSK Investigational SiteCerritos, United States
- GSK Investigational SiteHuntington Beach, United States
- GSK Investigational SiteSanta Clara, United States
- GSK Investigational SiteCooper City, United States
- GSK Investigational SiteCutler Bay, United States
- GSK Investigational SiteMiami, United States
- GSK Investigational SiteMiami, United States
- GSK Investigational SiteWichita, United States
- GSK Investigational SiteLouisville, United States
- GSK Investigational SiteNew Orleans, United States
- GSK Investigational SiteHenderson, United States
- GSK Investigational SiteWilliamsville, United States
- GSK Investigational SiteGreensboro, United States
- GSK Investigational SiteDuncansville, United States
- GSK Investigational SiteCharlottesville, United States
- GSK Investigational SiteBuenos Aires, Argentina
- GSK Investigational SiteBuenos Aires-San Isidro, Argentina
- GSK Investigational SiteCiudad Autonoma Buenos Aires, Argentina
- GSK Investigational SiteCiudad AutOnoma de Buenos Aire, Argentina
- GSK Investigational SiteCiudad Autonoma de Buenos Aire, Argentina
- GSK Investigational SiteMar del Plata, Argentina
- GSK Investigational SiteBotany, Australia
- GSK Investigational SiteKotara, Australia
- GSK Investigational SiteSydney, Australia
- GSK Investigational SiteCamberwell, Australia
And 68 more, listed on the interactive page.
Other registry identifiers
- 2022-502799-22-00