Clinical trial NCT05838742: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pain
Osteoarthritis, Knee
Keywords: Osteoarthritis
Musculoskeletal Diseases
209978
GSK3858279
Efficacy
Safety
Pharmacokinetics
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2023-05-03
Enrollment: 314
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline at Week 12 in weekly average of average daily knee pain intensity, assessed on the Numeric Rating Scale (NRS)
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change from Baseline at Week 12 in Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score
timeFrame: Baseline and Week 12
measure: Change from Baseline at Week 12 in WOMAC function subscale score
timeFrame: Baseline and Week 12
measure: Change from Baseline at Week 12 in patient global assessment of disease (PtGA)
timeFrame: Baseline and Week 12
measure: Number of participants with adverse events (AEs), serious AE (SAEs) and AEs of special interest (AESI)
timeFrame: Up to 31 weeks
measure: 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
measure: Maximum observed concentration (Cmax) of GSK3858279
timeFrame: At Week 12
measure: The amount of time for GSK3858279 to reach Cmax (tmax)
timeFrame: At Week 12
measure: Pre-dose (trough) concentration at the end of the dosing interval (Ctau) of GSK3858279
timeFrame: At Week 12
measure: Average concentration over a dosing interval (Cavg) of GSK3858279
timeFrame: At Week 12
measure: Area under the time-concentration curve (AUC) over the dosing interval (0-tau) (AUC[0-tau]) of GSK3858279
timeFrame: At Week 12
Other outcomes:
Locations:
city: Cerritos
country: United States
facility: GSK Investigational Site
state: California
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Santa Clara
country: United States
facility: GSK Investigational Site
state: California
city: Cooper City
country: United States
facility: GSK Investigational Site
state: Florida
city: Cutler Bay
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Henderson
country: United States
facility: GSK Investigational Site
state: Nevada
city: Williamsville
country: United States
facility: GSK Investigational Site
state: New York
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Duncansville
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Buenos Aires-San Isidro
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad AutOnoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
city: Botany
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Kotara
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Sydney
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Camberwell
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Victoria
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Guelph
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Winchester
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Joliette
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Trois-Rivieres
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Changchun
country: China
facility: GSK Investigational Site
city: Chengdu
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
city: Huhhot
country: China
facility: GSK Investigational Site
city: Nanjing
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shenyang
country: China
facility: GSK Investigational Site
city: Shijiazhuang
country: China
facility: GSK Investigational Site
city: Tianjin
country: China
facility: GSK Investigational Site
city: ZhuZhou
country: China
facility: GSK Investigational Site
city: Dax
country: France
facility: GSK Investigational Site
city: La Roche Sur Yon
country: France
facility: GSK Investigational Site
city: La Rochelle Cedex 1
country: France
facility: GSK Investigational Site
city: Montpellier cedex 5
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Magdeburg
country: Germany
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Shimane
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Chihuahua
country: Mexico
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
city: Merida
country: Mexico
facility: GSK Investigational Site
city: Mexicali
country: Mexico
facility: GSK Investigational Site
city: Torreon
country: Mexico
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
city: Gauteng
country: South Africa
facility: GSK Investigational Site
city: Johannesburg
country: South Africa
facility: GSK Investigational Site
city: Stellenbosch
country: South Africa
facility: GSK Investigational Site
city: A Coruna
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Blackpool
country: United Kingdom
facility: GSK Investigational Site
city: Cannock
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: