A Dose-Finding Study to Evaluate the Efficacy and Safety of GSK3858279 in Adults With Knee Osteoarthritis Pain

Pain Clinical Trial

— MARS-17  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05838742
• Other study ID #: 209978
• Secondary ID: 2022-502799-22-0
• Status: Recruiting
• Phase: Phase 2
• Start date: September 13, 2023
• Est. completion date: October 20, 2025

Study information

• Verified date: October 2023
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is dose-finding study of GSK3858279 in participants with moderate to severe knee osteoarthritis (OA) 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: October 20, 2025
• Est. primary completion date: July 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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 millilitre/ minute (mL/min)/1.73 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.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee
• Pain

Intervention

Drug:
• GSK3858279
GSK3858279 will be administered.
• Placebo
Placebo will be administered.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	San Isidro	Buenos Aires
Australia	GSK Investigational Site	Botany	New South Wales
Australia	GSK Investigational Site	Camberwell	Victoria
Australia	GSK Investigational Site	Campbelltown	New South Wales
Australia	GSK Investigational Site	Kotara	New South Wales
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Guelph	Ontario
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Saint-Charles-Borromée	Quebec
Canada	GSK Investigational Site	Sarnia	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
Canada	GSK Investigational Site	Victoria	British Columbia
Canada	GSK Investigational Site	Winchester	Ontario
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Chengdu	Sichuan
China	GSK Investigational Site	Guangzhou
China	GSK Investigational Site	Huhhot	Inner Mongolia
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Shijiazhuang City	Hebei
China	GSK Investigational Site	Tianjin
China	GSK Investigational Site	ZhuZhou	Hunan
France	GSK Investigational Site	Cahors
France	GSK Investigational Site	Dax
France	GSK Investigational Site	La Roche Sur Yon
France	GSK Investigational Site	La Rochelle
France	GSK Investigational Site	Montpellier
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Saint Priest en Jarez
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Rendsburg	Schleswig-Holstein
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Nagano
Japan	GSK Investigational Site	Nagano
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Shimane
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Seongnam-si
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Merida	Yucatán
Mexico	GSK Investigational Site	Mexicali	Baja California Norte
Mexico	GSK Investigational Site	Torreon	Coahuila
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Kempton Park
South Africa	GSK Investigational Site	Stellenbosch
Spain	GSK Investigational Site	A Coruna
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Centelles (Barcelona)
Spain	GSK Investigational Site	La Roca Del Valles (Barcelona)
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Pozuelo De Alarcón/Madrid
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Sevilla
United Kingdom	GSK Investigational Site	Barnet	Hertfordshire
United Kingdom	GSK Investigational Site	Blackpool	Lancashire
United Kingdom	GSK Investigational Site	Cannock	Staffordshire
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Norwich
United States	GSK Investigational Site	Cerritos	California
United States	GSK Investigational Site	Charlottesville	Virginia
United States	GSK Investigational Site	Cooper City	Florida
United States	GSK Investigational Site	Cutler Bay	Florida
United States	GSK Investigational Site	Duncansville	Pennsylvania
United States	GSK Investigational Site	Greensboro	North Carolina
United States	GSK Investigational Site	Henderson	Nevada
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	Sunnyvale	California
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Williamsville	New York

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  China,  France,  Germany,  Japan,  Korea, Republic of,  Mexico,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline at Week 12 in weekly average of average daily knee pain intensity, assessed on the Numeric Rating Scale (NRS)	To capture information on the self-reported average knee pain intensity in index knee, over the past 24 hours, participants will be asked to mark their average pain-intensity daily, using the NRS, on an 11-point scale (0-10), with 0 = no pain, and 10 = pain as bad as you can imagine. Daily scores for each participant will be averaged over 7 days to obtain a weekly score.	Baseline and Week 12
Secondary	Change from baseline at Week 12 in Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score	The WOMAC proprietary set of standardized questionnaires used by health professionals and to evaluate the condition of participants with osteoarthritis of the knee and hip, including pain, stiffness of the joints. The questionnaire covers pain, stiffness and function related to OA in the index knee over the past 48 hours. Participants will respond to each question using an 11- point NRS (0-10), with 0 = no pain/stiffness/difficulty, and 10 = extreme pain/stiffness/difficulty.	Baseline and Week 12
Secondary	Change from baseline at Week 12 in WOMAC function subscale score	The WOMAC is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of participants with osteoarthritis of the knee and hip, for physical functioning of the joints. The questionnaire covers pain, stiffness and function related to OA in the index knee over the past 48 hours. Participants will respond to each question using an 11- point NRS (0-10), with 0 = no pain/stiffness/difficulty, and 10 = extreme pain/stiffness/difficulty.	Baseline and Week 12
Secondary	Change from baseline at Week 12 in patient global assessment of disease (PtGA)	The PtGA is assessment of study participant for disease conditions and intensity of knee OA pain. Participants will respond on a Likert scale ranging from 1-5. Higher scores indicate worse condition.	Baseline and Week 12
Secondary	Occurrence of adverse events (AEs), serious AE (SAEs) and AEs of special interest (AESI)	AEs, SAEs, and AESIs will be collected. 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 SAE. AESIs of the study drug includes serious and opportunistic infections, tuberculosis (TB) and TB reactivation, serious hypersensitivity reactions and Injection site reactions.	Up to 31 weeks
Secondary	Change from Baseline in Haematology Parameters: neutrophils, lymphocytes, monocytes, eosinophils, basophils, white blood cell (WBC), and platelet count (Giga cells per liter)		Baseline and up to Week 31
Secondary	Change from Baseline in Haematology Parameters: Red blood cell (RBC) count, (Trillion cells per liter)		Baseline and up to Week 31
Secondary	Change from baseline in haematology parameter: Haemoglobin (Hb) (Grams per liter)		Baseline and up to Week 31
Secondary	Change from baseline in haematology parameter: Haematocrit (Proportion of red blood cells in blood)		Baseline and up to Week 31
Secondary	Change from baseline in clinical chemistry parameters: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), and Alkaline Phosphatase (AP) (International units per liter)		Baseline and up to Week 31
Secondary	Change from baseline in clinical chemistry parameter: Total bilirubin (Micromoles per liter)		Baseline and up to Week 31
Secondary	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)	Hematological/clinical chemistry abnormalities summarized according to NCI CTCAE grade	Up to 31 weeks
Secondary	Population parameters for the model describing the relationship between Dose, PK and response assessed on the NRS	Longitudinal dose-exposure-response (D-E-R) relationship between GSK3858279 dose, PK and weekly average of average daily knee pain intensity, assessed on the Numeric Rating Scale (NRS). Where the pain is scored on a 11-point scale (0-10), with 0 = no pain, and 10 = extreme pain as bad as you can imagine.	At Week 12
Secondary	Maximum observed concentration (Cmax) of GSK3858279	Cmax predicted from the D-E-R model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	At Week 12
Secondary	The amount of time for GSK3858279 to reach Cmax (tmax)	Tmax predicted from the D-E-R model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	At Week 12
Secondary	Pre-dose (trough) concentration at the end of the dosing interval (Ctau) of GSK3858279	Ctau predicted from the D-E-R model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	At Week 12
Secondary	Average concentration over a dosing interval (Cavg) of GSK3858279	Cavg predicted from the D-E-R model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	At Week 12
Secondary	Area under the time-concentration curve (AUC) over the dosing interval (0-tau) (AUC[0-tau]) of GSK3858279	AUC(0-tau) predicted from the D-E-R model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	At Week 12