A Study to Assess Efficacy and Safety of GLPG1972/S201086 in Participants With Knee Osteoarthritis

Osteoarthritis Clinical Trial

— Roccella  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03595618
• Other study ID #: GLPG1972-CL-201
• Secondary ID: 2017-004581-10U1
• Status: Completed
• Phase: Phase 2
• Start date: August 14, 2018
• Est. completion date: July 14, 2020

Study information

• Verified date: July 2021
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 932
• Est. completion date: July 14, 2020
• Est. primary completion date: July 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• GLPG1972
Film-coated tablets of GLPG1972 for oral use.
• Placebo
Film-coated tablets of matching placebo for oral use.

Locations

Country	Name	City	State
United States	Achieve Clinical Research, LLC	Birmingham	Alabama
United States	Central Research Associates, Inc.	Birmingham	Alabama
United States	Millennium Pain Center - Bloomington	Bloomington	Illinois
United States	Injury Care Research, LLC	Boise	Idaho
United States	Tufts Medical Center	Boston	Massachusetts
United States	NY Scientific	Brooklyn	New York
United States	Charlottesville Medical Research Center, LCC	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Optimed Research, LTD	Columbus	Ohio
United States	Samy Metyas MD, Inc - Covina Arthritis Clinic	Covina	California
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	TriWest Research Associates, LLC	El Cajon	California
United States	Medisphere Medical Research Center	Evansville	Indiana
United States	Lillestol Research, LCC	Fargo	North Dakota
United States	Clinical Physiology Associates Clinical Study Center	Fort Myers	Florida
United States	Pioneer Research Solutions Inc.	Houston	Texas
United States	Health Awareness, Inc	Jupiter	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	BioSolutions Clinical Research Center	La Mesa	California
United States	The Helm Center for Pain Management	Laguna Hills	California
United States	Clinical Research Consortium Nevada	Las Vegas	Nevada
United States	Central Kentucky Research Associates, Inc.	Lexington	Kentucky
United States	Medpharmics	Metairie	Louisiana
United States	Center for Musculoskeletal Care - Yale Medicine	New Haven	Connecticut
United States	Health Research of Hampton Roads, Inc. - Newport News	Newport News	Virginia
United States	Clinical Research Associates of Tidewater	Norfolk	Virginia
United States	Bioclinica Research	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Arizona Research Center	Phoenix	Arizona
United States	Elite Clinical Studies	Phoenix	Arizona
United States	Hope Research Institute, LLC - Arizona	Phoenix	Arizona
United States	Phoenix Medical Reasearch	Prairie Village	Kansas
United States	Rochester Clinical Research, Inc.	Rochester	New York
United States	Diagnostics Research Group	San Antonio	Texas
United States	Artemis Institute for Clinical Research - San Diego	San Diego	California
United States	Artemis Institute for Clinical Research - San Marcos	San Marcos	California
United States	Encompass Clinical Research	Spring Valley	California
United States	Stedman Clinical Trials, LLC	Tampa	Florida
United States	Clinical Research Consortium Arizona	Tempe	Arizona
United States	Compass Research, LLC	The Villages	Florida
United States	Advanced Clinical Research	West Jordan	Utah
United States	The Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	Upstate Clinical Research Associates	Williamsville	New York

Sponsors (2)

Lead Sponsor	Collaborator
Galapagos NV	Institut de Recherches Internationales Servier

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee to Week 52	Reduction in cartilage loss was assessed by cartilage thickness as measured in the medial cMTFC of the target knee using qMRI.	Baseline, Week 52
Secondary	Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee	A "structural progressor" was defined as a participant who had an 8% cartilage loss in cMTFC. Number of participants who met the criteria of "structural progressor" at Week 52 are provided.	Week 52
Secondary	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	Western Ontario and McMaster Universities Osteoarthritis Index is a questionnaire designed to assess health status and health outcomes in participants with OA of the knee. The questionnaire contains 24 questions targeting areas of pain, stiffness, and physical function. Pain subscale includes 5 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-20 with higher scores indicating worse symptoms and function. Stiffness subscale includes 2 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-8 with higher scores indicating worse symptoms and function. Physical function subscale includes 17 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-68 with higher scores indicating worse symptoms and function. The total score is the sum of all subscales (range: 0 to 96) with higher scores indicating worse symptoms and function.	Baseline, Week 52
Secondary	Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52	The participant was asked "how would you rate the pain felt in the selected knee within the last 48 hours?". The participants rated the pain by marking the level of pain on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher pain intensity.	Baseline, Week 52
Secondary	Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52	The participant was asked "Considering all the ways in which your knee osteoarthritis affects you, please rate on this 100 mm scale how well you are doing today". The participants rated the disease activity by marking on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher disease activity.	Baseline, Week 52
Secondary	Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria	OMERACT-OARSI criteria involves improvement based on WOMAC pain and function subscales and PGA. The responders according to OMERACT-OARSI criteria were participants who had: A high improvement in pain or in function = 50% and absolute change = 20, OR; Improvement in at least 2 of the 3 following: Pain = 20% and absolute change = 10; Function = 20% and absolute change = 10; Patient's global assessment = 20% and absolute change = 10.; WOMAC pain subscale score: range of 0 to 20, higher scores indicating more pain,; WOMAC physical function subscale score: range of 0 to 68, higher scores indicating worse physical function),; PGA: The participant was asked "Considering all the ways in which your knee osteoarthritis affects you, please rate on this 100 mm scale how well you are doing today". The participants rated disease activity by marking on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher disease activity.	Week 52
Secondary	Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52	Reduction of cartilage loss was measured by cartilage thickness of the tTFC of the target knee using qMRI.	Baseline, Week 52
Secondary	Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28		Baseline, Week 28
Secondary	Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52		Baseline, Week 52
Secondary	Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52	The JSW is the space measured between the 2 bones in the knee joint and this is assessed by x-ray.	Baseline, Week 52
Secondary	Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study	Systemic analgesics included anti-inflammatory and anti-rheumatic products; analgesics; anti-diarrheals, intestinal, anti-inflammatory/anti-infective agents; and drugs for functional gastrointestinal disorders.	Baseline up to Week 52
Secondary	Plasma Concentrations of GLPG1972		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
Secondary	Number of Participants With Treatment-emergent Adverse Event (TEAE)	TEAEs were defined as all adverse events (AEs) that occurred: between first IMP intake date (included) and last visit of participant, or; before first IMP intake date and that worsened (in terms of intensity) or became serious according to investigator opinion between first IMP intake date (included) and last visit of participant.; Number of participants with at least 1 TEAE (serious or non-serious) are reported.	Baseline up to 2-weeks after last dose of IMP (up to Week 54)