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

JRCT ID: jRCT2031230411

Registered date:18/10/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Pain due to knee osteoarthritis
• Date of first enrollment: 27/11/2023
• Target sample size: 420
• Countries of recruitment: Australia,Japan,Argentina,Japan,Canada,Japan,China,Japan,France,Japan,Germany,Japan,Korea,Japan,Mexico,Japan,South Africa,Japan,Spain,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

-GSK3858279 (4 doses)
-Placebo
This study consists of 5 study arms (Placebo arm and GSK3858279 dose1~4 arms).

Outcome(s)

• Primary Outcome: Change from baseline at Week 12 in weekly average of average daily knee pain intensity, assessed on the Numeric Rating Scale (NRS)

Secondary Outcome

- Change from baseline at Week 12 in Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score
- Change from baseline at Week 12 in WOMAC function subscale score
- Change from baseline at Week 12 in patient global assessment of disease (PtGA)
- Occurrence of adverse events (AEs), serious AE (SAEs) and AEs of special interest (AESI)
- Change from Baseline in Haematology Parameters: neutrophils, lymphocytes, monocytes, eosinophils, basophils, white blood cell (WBC), and platelet count (Giga cells per liter), Red blood cell (RBC) count, (Trillion cells per liter), Haemoglobin (Hb) (Grams per liter), Haematocrit (Proportion of red blood cells in blood)
- Change from baseline in clinical chemistry parameters: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), and Alkaline Phosphatase (AP) (L167International units per liter), Total bilirubin (Micromoles per liter)
- 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)
- Population parameters for the model describing the relationship between Dose, PK and response assessed on the NRS
- Maximum observed concentration (Cmax) of GSK3858279 [ Time Frame: At Week 12 ]
The amount of time for GSK3858279 to reach Cmax (tmax) [ Time Frame: At Week 12 ]
Pre-dose (trough) concentration at the end of the dosing interval (Ctau) of GSK3858279 [ Time Frame: At Week 12 ]
Average concentration over a dosing interval (Cavg) of GSK3858279 [ Time Frame: At Week 12 ]
Area under the time-concentration curve (AUC) over the dosing interval (0-tau) (AUC[0-tau]) of GSK3858279 [ Time Frame: At Week 12 ]

Key inclusion & exclusion criteria

• Age minimum: >= 40age old
• Age maximum: <= 80age old
• Gender: Both

Include 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.

Exclude 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 Information

• Primary Sponsor: Okawa Yasutoshi
• Secondary ID(s): NCT05838742