A Dose-Finding Study to Evaluate the Efficacy and Safety of GSK3858279 in Adults With Knee Osteoarthritis (OA) Pain (MARS-17)

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

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.

Study Overview

• Status: Terminated
• Conditions: Pain; Osteoarthritis, Knee
• Intervention / Treatment: Drug: Placebo; Drug: GSK3858279

• Study Type: Interventional
• Enrollment (Actual): 314
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1128AAF
    • GSK Investigational Site
  • Buenos Aires-San Isidro, Argentina, 1643
    • GSK Investigational Site
  • Ciudad AutOnoma de Buenos Aire, Argentina, 1118
    • GSK Investigational Site
  • Ciudad Autonoma Buenos Aires, Argentina, C1417
    • GSK Investigational Site
  • Ciudad Autonoma de Buenos Aire, Argentina, C1046AAQ
    • GSK Investigational Site
  • Mar del Plata, Argentina, B7600FYK
    • GSK Investigational Site
• Australia
  • New South Wales
    • Botany, New South Wales, Australia, 2019
      • GSK Investigational Site
    • Kotara, New South Wales, Australia, 2289
      • GSK Investigational Site
    • Sydney, New South Wales, Australia, 2010
      • GSK Investigational Site
  • Victoria
    • Camberwell, Victoria, Australia, 3124
      • GSK Investigational Site
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 4A1
      • GSK Investigational Site
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • GSK Investigational Site
    • Guelph, Ontario, Canada, N1H 1B1
      • GSK Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5T 2S8
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M9V 4B4
      • GSK Investigational Site
    • Winchester, Ontario, Canada, K0C 2K0
      • GSK Investigational Site
  • Quebec
    • Joliette, Quebec, Canada, J6E 6A9
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • GSK Investigational Site
    • Trois-Rivières, Quebec, Canada, G9A 3X2
      • GSK Investigational Site
• China
  • Beijing, China, 100730
    • GSK Investigational Site
  • Beijing, China, 100083
    • GSK Investigational Site
  • Changchun, China, 130021
    • GSK Investigational Site
  • Chengdu, China, 610041
    • GSK Investigational Site
  • Guangzhou, China, 510000
    • GSK Investigational Site
  • Hohhot, China, 010017
    • GSK Investigational Site
  • Nanjing, China, 210009
    • GSK Investigational Site
  • Shanghai, China, 200040
    • GSK Investigational Site
  • Shanghai, China, 200065
    • GSK Investigational Site
  • Shanghai, China, 200011
    • GSK Investigational Site
  • Shenyang, China, 110022
    • GSK Investigational Site
  • Shijiazhuang, China, 050051
    • GSK Investigational Site
  • Tianjin, China, 300192
    • GSK Investigational Site
  • Zhuzhou, China, 412007
    • GSK Investigational Site
• France
  • Dax, France, 40107
    • GSK Investigational Site
  • La Roche-sur-Yon, France, 85925
    • GSK Investigational Site
  • La Rochelle, France, 17019
    • GSK Investigational Site
  • Montpellier, France, 34000
    • GSK Investigational Site
  • Paris, France, 75012
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10117
    • GSK Investigational Site
  • Hamburg, Germany, 22415
    • GSK Investigational Site
  • Hamburg, Germany, 20095
    • GSK Investigational Site
  • Magdeburg, Germany, 39120
    • GSK Investigational Site
• Japan
  • Fukuoka, Japan, 834-0115
    • GSK Investigational Site
  • Ibaraki, Japan, 300-1234
    • GSK Investigational Site
  • Ibaraki, Japan, 300-1253
    • GSK Investigational Site
  • Nagano, Japan, 390-8601
    • GSK Investigational Site
  • Nagano, Japan, 395-8505
    • GSK Investigational Site
  • Osaka, Japan, 543-0027
    • GSK Investigational Site
  • Saitama, Japan, 330-0074
    • GSK Investigational Site
  • Shimane, Japan, 693-8501
    • GSK Investigational Site
  • Tokyo, Japan, 103-0027
    • GSK Investigational Site
  • Tokyo, Japan, 113-8431
    • GSK Investigational Site
  • Tokyo, Japan, 104-0031
    • GSK Investigational Site
• Mexico
  • Chihuahua City, Mexico, 31000
    • GSK Investigational Site
  • Guadalajara, Mexico, 44650
    • GSK Investigational Site
  • Mexicali, Mexico, 21200
    • GSK Investigational Site
  • Mérida, Mexico, CP 97070
    • GSK Investigational Site
  • Torreón, Mexico, 27000
    • GSK Investigational Site
• South Africa
  • Cape Town, South Africa, 7405
    • GSK Investigational Site
  • Cape Town, South Africa, 7130
    • GSK Investigational Site
  • Gauteng, South Africa, 1619
    • GSK Investigational Site
  • Johannesburg, South Africa, 2113
    • GSK Investigational Site
  • Stellenbosch, South Africa, 7600
    • GSK Investigational Site
• South Korea
  • Seoul, South Korea, 03080
    • GSK Investigational Site
  • Seoul, South Korea, 06973
    • GSK Investigational Site
  • Seoul, South Korea, 07441
    • GSK Investigational Site
• Spain
  • A Coruña, Spain, 15006
    • GSK Investigational Site
  • Barcelona, Spain, 08540
    • GSK Investigational Site
  • Barcelona, Spain, 08430
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Santander, Spain, 39008
    • GSK Investigational Site
  • Santiago de Compostela, Spain, 15702
    • GSK Investigational Site
  • Seville, Spain, 41014
    • GSK Investigational Site
• United Kingdom
  • Blackpool, United Kingdom, FY2 0JH
    • GSK Investigational Site
  • Cannock, United Kingdom, WS11 0BN
    • GSK Investigational Site
  • London, United Kingdom, EN5 3DJ
    • GSK Investigational Site
  • Manchester, United Kingdom, M13 9NQ
    • GSK Investigational Site
• United States
  • California
    • Cerritos, California, United States, 90703
      • GSK Investigational Site
    • Huntington Beach, California, United States, 92647
      • GSK Investigational Site
    • Santa Clara, California, United States, 95054
      • GSK Investigational Site
  • Florida
    • Cooper City, Florida, United States, 33024
      • GSK Investigational Site
    • Cutler Bay, Florida, United States, 33189
      • GSK Investigational Site
    • Miami, Florida, United States, 33173
      • GSK Investigational Site
    • Miami, Florida, United States, 33185
      • GSK Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67207
      • GSK Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • GSK Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • GSK Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89052
      • GSK Investigational Site
  • New York
    • Williamsville, New York, United States, 14221
      • GSK Investigational Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27410
      • GSK Investigational Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • GSK Investigational Site
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK3858279 - 60 mg weekly; Participants received GSK3858279 60 milligram (mg) SC injection once per week for 16 weeks.	Drug: GSK3858279; GSK3858279 will be administered.
Experimental: GSK3858279 - 240 mg every 2 weeks; Participants received GSK3858279 240 mg SC injection every other week for 16 weeks. Placebo was given in the intervening week to maintain the blinding.	Drug: GSK3858279; GSK3858279 will be administered.
Experimental: GSK3858279 - 240 mg weekly; Participants received GSK3858279 240 mg SC injection once per week for 16 weeks.	Drug: GSK3858279; GSK3858279 will be administered.
Experimental: GSK3858279 - 360 mg weekly; Participants received GSK3858279 360 mg SC injection once per week for 16 weeks.	Drug: GSK3858279; GSK3858279 will be administered.
Placebo Comparator: Placebo; Participants received placebo subcutaneous (SC) injection once per week for 16 weeks	Drug: Placebo; Placebo will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Average of Average Daily Knee Pain Intensity Using Numeric Rating Scale 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.	Baseline (Day -7 to Day -1) and at Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score 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.	Baseline (Day 1) and at Week 12
Change From Baseline in WOMAC Physical Function Subscale Score 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.	Baseline (Day 1) and at Week 12
Change From Baseline in Patient Global Assessment Of Disease (PtGA) 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.	Baseline (Day 1) and at Week 12
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESI)	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.	Up to 31 weeks
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)	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.	Up to 31 weeks
Maximum Concentration (Cmax) of GSK3858279	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.	Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12
Time to Maximum Plasma Concentration (Tmax) of GSK3858279	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: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12
Pre-Dose (Trough) Concentration at the End of the Dosing Interval (Ctau) of GSK3858279	Ctau predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12
Average Concentration Over a Dosing Interval (Cavg) of GSK3858279	Cavg predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12
Area Under the Time-Concentration Curve (AUC) Over the Dosing Interval (0-Tau) (AUC[0-Tau]) of GSK3858279	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.	Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2023
• Primary Completion (Actual): August 12, 2024
• Study Completion (Actual): December 3, 2024

Study Registration Dates

• First Submitted: April 20, 2023
• First Submitted That Met QC Criteria: April 20, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: October 24, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Osteoarthritis; Efficacy; Pharmacokinetics; Musculoskeletal Diseases; GSK3858279; 209978
• Additional Relevant MeSH Terms: Neurologic Manifestations; Arthritis; Joint Diseases; Rheumatic Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Osteoarthritis; Osteoarthritis, Knee; Musculoskeletal Diseases
• Other Study ID Numbers: 209978; 2022-502799-22-00 (Other Identifier: EU-CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No