Clinical trial NCT03595618: A Study to Assess Efficacy and Safety of GLPG1972/S201086 in Participants With Knee Osteoarthritis
Official title: Efficacy and Safety of 3 Doses of S201086/GLPG1972 Administered Orally Once Daily in Patients With Knee Osteoarthritis. A 52-week International, Multi-regional, Multi-center, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
Collaborators: name: Institut de Recherches Internationales Servier
First posted: 2018-07-23
Enrollment: 932
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a phase 2, 52-week international, multi-regional, multi-center, randomized, double-blind, placebo-controlled dose-ranging study for the treatment of osteoarthritis.


Eligibility criteria: Inclusion Criteria:

* Male participants or female participants of non-childbearing potential and not breastfeeding.
* Body weight \> 40 kg, body mass index (BMI) \< 40 kg/m\^2.
* Diagnosed for knee osteoarthritis based on clinical and radiological criteria of the American College of Rheumatology.
* History of knee pain for at least 6 months and on the majority of days (\> 50%) during the preceding month.
* Symptom severity defined by a pain ≥ 40 mm and ≤ 90 mm on visual analogue scale (VAS, 100 mm) at screening and inclusion visits.
* Documented need for symptomatic as needed-treatment for osteoarthritis (OA) in the target knee with systemic non-steroidal anti-inflammatory drugs (NSAIDs) and/or other analgesics

Exclusion Criteria:

* Severe clinical knee malalignment according to the investigator.
* Knee prosthesis already implanted (\< 1 year) or not well-tolerated (contralateral side).
* Knee prosthesis already foreseen within the study period (whichever side).
* Hip prosthesis recently implanted (\< 1 year) or foreseen within the study period (whichever side).
* Previous osteotomy on the inferior limbs (whichever side).
* Surgical operation on the target knee within the 12 months prior to the screening visit or planned during the study.
* Diagnostic arthroscopy of the target knee within the 6 months prior to the screening visit or planned during the study.
* Other pathologies affecting the target knee.
* Any contraindication to magnetic resonance imaging (MRI) including the inability to undergo a knee MRI exam because of inability to fit in the scanner or knee coil.

Primary outcomes:
measure: Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee to Week 52
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee
timeFrame: Week 52
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52
timeFrame: Baseline, Week 52
measure: Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria
timeFrame: Week 52
measure: Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52
timeFrame: Baseline, Week 52
measure: Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study
timeFrame: Baseline up to Week 52
measure: Plasma Concentrations of GLPG1972
timeFrame: Pre-dose at Weeks 4, 12, and 52; Pre-dose and one post-dose sample (2-4 hours interval) at Week 28; one post dose sample (interval 4-8 hours) at Week 40
measure: Number of Participants With Treatment-emergent Adverse Event (TEAE)
timeFrame: Baseline up to 2-weeks after last dose of IMP (up to Week 54)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Research Associates, Inc.
state: Alabama
city: Birmingham
country: United States
facility: Achieve Clinical Research, LLC
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies
state: Arizona
city: Phoenix
country: United States
facility: Hope Research Institute, LLC - Arizona
state: Arizona
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Consortium Arizona
state: Arizona
city: Covina
country: United States
facility: Samy Metyas MD, Inc - Covina Arthritis Clinic
state: California
city: El Cajon
country: United States
facility: TriWest Research Associates, LLC
state: California
city: La Mesa
country: United States
facility: BioSolutions Clinical Research Center
state: California
city: Laguna Hills
country: United States
facility: The Helm Center for Pain Management
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research - San Diego
state: California
city: San Marcos
country: United States
facility: Artemis Institute for Clinical Research - San Marcos
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: New Haven
country: United States
facility: Center for Musculoskeletal Care - Yale Medicine
state: Connecticut
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Fort Myers
country: United States
facility: Clinical Physiology Associates Clinical Study Center
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials, LLC
state: Florida
city: The Villages
country: United States
facility: Compass Research, LLC
state: Florida
city: Boise
country: United States
facility: Injury Care Research, LLC
state: Idaho
city: Bloomington
country: United States
facility: Millennium Pain Center - Bloomington
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Evansville
country: United States
facility: Medisphere Medical Research Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Prairie Village
country: United States
facility: Phoenix Medical Reasearch
state: Kansas
city: Lexington
country: United States
facility: Central Kentucky Research Associates, Inc.
state: Kentucky
city: Metairie
country: United States
facility: Medpharmics
state: Louisiana
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Las Vegas
country: United States
facility: Clinical Research Consortium Nevada
state: Nevada
city: Brooklyn
country: United States
facility: NY Scientific
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates
state: New York
city: Fargo
country: United States
facility: Lillestol Research, LCC
state: North Dakota
city: Columbus
country: United States
facility: Optimed Research, LTD
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Houston
country: United States
facility: Pioneer Research Solutions Inc.
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center, LCC
state: Virginia
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc. - Newport News
state: Virginia
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
Study officials:
affiliation: Galapagos NV
name: Galapagos Study Director
role: STUDY_DIRECTOR
References:
citation: Brebion F, Gosmini R, Deprez P, Varin M, Peixoto C, Alvey L, Jary H, Bienvenu N, Triballeau N, Blanque R, Cottereaux C, Christophe T, Vandervoort N, Mollat P, Touitou R, Leonard P, De Ceuninck F, Botez I, Monjardet A, van der Aar E, Amantini D. Discovery of GLPG1972/S201086, a Potent, Selective, and Orally Bioavailable ADAMTS-5 Inhibitor for the Treatment of Osteoarthritis. J Med Chem. 2021 Mar 25;64(6):2937-2952. doi: 10.1021/acs.jmedchem.0c02008. Epub 2021 Mar 15.